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spk13: Good day everyone and thank you for standing by. Welcome to the Acadia
spk05: Pharmaceuticals first quarter 2024 financial results and operating overview conference call.
spk13: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be
spk05: a question and answer session. To participate, you will need to press star 1-1 on your telephone. You will then hear a message
spk13: advising your hand is raised. To withdraw the question, press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Al Kildany, senior vice president of investor relations and corporate communications. Please proceed.
spk03: Thank you. Good afternoon and thank you for joining us on today's call to discuss Acadia's first quarter 2024 earnings. Joining me on the call today from Acadia are Steve Davis, our chief executive officer who will provide some opening remarks, followed by Brendan Tian, our chief operating officer and head of commercial, who will discuss our strong commercial franchises, Debut and New Plaza. Also joining us is Kimberly Mannhard, senior vice president of global strategic planning and execution who will provide an update on our pipeline programs. And Mark Schneier,
spk05: our chief financial officer who will review financial highlights. Steve, we will have a few minutes before we
spk03: open the call up for your questions. In addition, Parag Nuswani, senior vice president of triphenotype rare disease franchise will be available for the Q&A session. We are using supplemental slides which are available on our website's events and presentations section. Before we go further proceeding, I would like to remind you that during our call today, we will be having a Q&A session and we will be making several forward looking statements within the meaning of the private securities litigation reform act of 1995. These forward looking statements, including goals, expectations, plans, prospects, growth potential, timing of events or future results are based on current information assumptions and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results. These factors and other risks associated with our business can be found in our filings made with the SEC. You are cautioned not to place undue reliance on these forward looking statements which are made only as of today's date. I'll now turn the call over to Steve for opening remarks. Thank you, Al. Good afternoon, everyone, and thank you for joining us. Please turn to slide five. The foundation of the KD's strategy for the KD's business is built on our two first in class drugs on the market, a robust pipeline of late stage assets with more behind them in a strong balance sheet that allows us to invest in future growth. During the first quarter, our commercial franchises delivered total revenues of $205.8 million, increasing 74% from the first quarter of 2023, which did not yet include sales at Bayview. Duplassit remains a strong cashflow that
spk05: generated a significant margin for franchise assets that delivered first quarter sales of $129
spk03: .99 million, up 10% from the first quarter of last year, as we continued to grow volume and gain share in the Parkinson's disease psychosis sector. We look forward to expanding on this growth. Sales of Bayview were $75.9 million in the first quarter, our first time completing this calendar period since our April 2023 launch. As we'll discuss on this call, one year into the launch, approximately one in four diagnosed red patients have initiated therapy with Bayview. The remaining three quarters of diagnosed patients and those not yet diagnosed represent a very large opportunity to continue to grow this drug and to reach families not yet benefiting from the only drug approved to treat Rett syndrome.
spk05: We also
spk03: have a number of other under-reported drug-related commercial franchises. We have a deep and growing
spk05: pipeline,
spk03: including our Phase III Prader-Willi syndrome program and our seamless Phase II, Phase III program in Alzheimer's disease psychosis. Acadia continues to operate from a position of financial strength. Revenues from our two commercial franchises enabled us to add $30 million to our cash position in the first quarter, which is traditionally a seasonally weak quarter of the year in our industry. As a result, we continue to remain a very strong balance sheet with a total cash of $470.5 million as of March 31st. Turning to slide six, I'll now provide a high-level update on Debut that both Brendan and Mark will expand on in their sections. We've just completed one year into the launch of Debut. Let me take a moment to recap where we stand today.
spk05: As you know, after launch,
spk03: we experienced a surge in patients that initiated their big quickly in the first several months of Debut's availability. As I referenced a moment ago, we have a sizable population to continue building share. Out of 5,000 diagnosed red patients in the US, as I mentioned, approximately one in four of these patients have initiated therapy with Debut. In addition, we believe the prevalent population of red patients in the US is between 6,000 and 9,000 patients. We expect as Debut is on the market longer, we will see more and more of the undiagnosed patients get diagnosed. Importantly, we continue to see real-world persistency rates track about 10 percentage points above the time-based rates of persistency observed in the most relevant populations from our clinical studies. We believe that on average, the dose patients take following any period of titration up
spk05: or down is approximately 70 to 85% of the labor dose.
spk03: Today,
spk05: we've established
spk03: a very broad prescriber base with over 650 individual writers. Brendan will speak to the shift in mix of prescriptions we've observed since launch, together with our expectations going forward. We've established a broad access to Debut with over 80% of red lives covered and conversion metrics that are consistent with industry norms and seasonality. Let me turn to a few of the key dynamics we see today as we enter our second year on the market. In the last year, we've now accumulated a substantial body of real-world experience with Debut. We're seeing more and more stories shared on both the medical and caregiver communities regarding the benefits of Debut, including
spk05: alertness, engagement, engagement, communication, and motor benefits.
spk03: On the dosing and GI management front, while our data indicate the average dose patients take longer term continues to be in the 75 to 80% range, we are seeing some variability in the application of strategies for titration and dose adjustments getting to the longer term dose. This represents an opportunity where we are focused on supporting dialogue in both the medical and caregiver communities regarding the establishment of consistent application of GI management strategies and best practices. Brendan will speak to both the benefits of Debut and GI management practices in his section. During most of the first quarter, we saw a decline in active patients on therapy as we experienced first-time seasonal dynamics together with an increase in numerical
spk05: discontinuations. In the first quarter, we saw a decrease in patient numbers, which is primarily associated with the higher rate of new patient starts
spk03: in the preceding two quarters. In other words, there is somewhat of a lag between numerical new patient starts and numerical discontinuations. Just to be clear, our overall
spk05: rate of persistency continues to track well above our clinical trial experience despite the fluctuation of the situation of numerical discontinuations we see in any given month or
spk03: quarter. Importantly, we now see net patient additions in each of the last six weeks and believe the lag-based increase in numerical discontinuations we observed in the first quarter has peaked and is now largely digested. To recap,
spk05: on debut, one of the most important years of the launch, we've established very healthy share with one in four diagnosed patients on therapy. Key long-term value drivers include a very large opportunity
spk03: to continue adding share and rates of persistency. We track approximately 10 percentage points above our clinical trial experience
spk05: and
spk03: are supported by a large prescribing
spk05: population and broad payback. Let's turn to a snapshot of our current products and pipeline and pipelines on slide seven. New plans as it continues to contribute substantial revenues and share growth,
spk03: furthering our strategic objective of optimizing cash flow in this franchise. In addition to our two successful commercial franchises, we have numerous late and early stage
spk05: pipeline assets representing important opportunities. These include
spk06: we increased Yew-Waye a ton of large work before weGo down along the . . . . . . . . .
spk05: . We're currently enrolling subjects in our syndrome. We're currently enrolling subjects in our phase three study. Part of willy is a rare and debilitating genetic disease where patients have an unrelenting drive to eat called hyproprifation. Sadly, the severity of this disorder translates into an average lifespan of only
spk03: 30 years. Here, too, there are no FDA approved treatments. We are currently enrolling our seamless phase II, phase III program with ACP204 in Alzheimer's disease psychosis patients, and there is no other disorder where there are no approved treatments. ACP204 is
spk05: our
spk03: second generation 5-HT2A blocker where we are leveraging our learnings from PIM advance.
spk05: And behind that, we have a rich package of powerful, non-invasive, early stage, early stage and early stage disclosed and undisclosed programs that will help position us for future growth. I will now turn it over to Brendan to discuss our commercial performance. And we will begin on slide 8. Thank you, Steve. Please turn to slide 8, beginning with debut. Let me start by discussing the three key drivers of long-term value for daily use and
spk06: long
spk05: -term value for long-term value for daily use. And continue to grow the potential they represent. First, with now
spk04: one out of four diagnosed RET patients having received
spk05: treatment with
spk04: ACP204, we still have a large remaining patient population in the market that has significantly higher physician and caregiver awareness about the product one year post-approval. Launched to date, we've been successful penetrating centers of excellence where we now have approximately 50% share of patients treated. So we have a lot of room to grow to
spk06: pursue growth to pursue in this
spk04: segment.
spk06: In addition,
spk04: we're also focusing on driving depth of prescribing outside of COEs. Where the majority of our patient potential exists. We're already seeing a shift in the source of prescriptions today and expect an increasing share to come from noncenter of excellence high volume institutions and community practices moving forward. Second, a year into launch, we now have a foundation of real-world evidence providing us the following levers. Number one is real-world benefits. We are describing the real-world
spk05: benefits patients and families are seeing across a wide range of diseases as well as the various types of diseases and diseases. Serving as
spk04: examples of successful treatment with Dave View. In a moment, I will share some quotes from caregivers about the meaningful benefits they're seeing in their patients. Number two is GI management. We're sharing key learning strategies and successful GI management strategies. We've observed a wide range of GI management approaches and we see an opportunity to further enhance and accelerate the establishment of best practices in the
spk05: community. Number three is that time to benefit is a key consideration. We know a majority of patients with their doctor's guidance are starting treatment by tight training. And of course, when you try to do tight training over a period of several weeks, it may take a little bit longer. It's therefore important to ensure that families and physicians have the right expectations regarding
spk04: the time it may take to observe benefits. We have observed that many discontinuations happen early in a patient's treatment, a timeframe that may not have been sufficient to get to a dose that produces benefits or work out an appropriate GI management.
spk05: To
spk04: further support these families, our messaging on treatment expectations emphasizes the importance of HCPs and the appropriate timeline to realize the benefits of debut and determine the appropriate GI management strategy for each patient. Our third driver is persistency on therapy. We now have data out to the nine-month mark that demonstrates persistency tracking 10 percentage points above what was observed in the LILAC open label extension study for placebo rollover patients. This continues the consistent persistency curve we've seen from the time of launch. I'd like to take a deeper dive into each of these drivers.
spk06: First,
spk04: let's discuss
spk05: market penetration and growth potential. When you're into launch, we've started
spk04: to see more than 1,300 patients on debut in a market with 5,000 diagnosed RET patients. Many of these patients come from COEs where we have approximately 50% patient share, which leaves us ample opportunity for growing in that setting. Our mix is shifting to an even more split of prescriptions, with one-third of prescriptions coming from centers of excellence, one-third from noncenter of excellence high-volume institutions, and one-third from community practices. Since the level of experience with treating RET patients outside of centers of excellence is lower, we're delivering enhanced messaging to these prescribers on both clinical benefits to expect from debut as well as tolerability management strategies. Our second key driver is the real-world evidence and
spk05: the success stories those...
spk04: ...to motivate both HCPs and families to initiate debut. Broad prescribing early post-launch has led to many debut treatment success stories across a range of ages and disease severities. We're now utilizing these successes to educate prescribers and caregivers on what to expect when starting and staying on debut, which will encourage broader adoption. Looking at GI management strategies, we've seen a pretty wide range of approaches. Some physicians and practices, particularly a few of the COEs, feel they have this very much dialed in, utilizing product labeling and GI management strategies
spk05: to
spk04: achieve
spk05: success. However, implementing the -the-matter application of these strategies in the broader community is variable. Telling us there is an important opportunity to educate further on these together-side lines. While we continue to be very encouraged by the longitudinal rate of persistence, we
spk04: believe that in addition to communicating debut's clinical benefits, implementation of the more consistent best practices in GI management will further support building a sizable base of enduring patients over time. This leads to our
spk05: next driver, persistency. We're really seeing a very consistent pattern in the very consistent pattern of post-launch launch
spk04: Let me now share our latest persistency data. With patient cohorts now out to nine months, the real-world persistency rate is 58%. Compared with 47%,
spk05: which is seen for placebo role over patients, in live lack of patient in nine months. As we described on
spk04: our
spk05: last call, approximately
spk04: 40% of patients that initiated therapy on debut in Phase 3 remain on therapy today. And I've been on
spk05: therapy for more than two and a half years. This comparison underscores the opportunity we see to build a sizable enduring population on debut. If we can continue to track approximately
spk04: 10% points above our clinical
spk05: trial experience, we believe the enduring population could be approximately half of patients who initiate therapy. Let me touch on the number of patients we have on therapy. As
spk04: of the week ending May 3rd, we have 862 patients active on debut therapy compared with the figures we shared on February 27th of 860.
spk05: In the first quarter, we
spk06: saw a
spk05: decline
spk04: in
spk05: active
spk04: patients on therapy due in part to an increase in numerical discontinuations Steve described earlier. We've now seen net patient additions in each of the last six weeks, and we believe the increase in numerical discontinuation we observed in the first quarter has peaked and is now largely digested. I'd like to recap our view of the US opportunity as we now commence our second year on the market. With over 3,500 diagnosed patients who have not yet tried debut and several thousand patients who have not yet been diagnosed, we have an opportunity to continue to substantially grow debut. Our persistency experience to date indicates we can build a sizable enduring population benefiting from debut. We have a strong foundation to build
spk05: on, including a large population that is growing from a private driving copy of the US population and broad payer access.
spk04: Please turn to slide 10 for a discussion of our plans on debut outside the United States. Looking beyond the US, we are rapidly advancing toward making debut available in additional markets. Our pediatric investigation plan or PIP, which detailed the previously completed clinical trials for debut, has been agreed upon with the pediatric committee of the EMA, paving the way for an anticipated filing in the first quarter of 2025.
spk05: In Japan, we now have a formal meeting scheduled with the PMDA later this quarter to discuss our proposed clinical plan. And in Canada, we recently announced that our new drug submission was accepted for filing and granted priority review by Health Canada,
spk04: potentially leading to an approval in that market around the end of this year. Let's now turn to slide 11. Here you see quotes from caregivers reinforcing some of the observations described above, each consistent with the
spk05: feedback we've
spk04: been hearing for many months. Such as caregivers
spk05: noting
spk04: higher levels of engagement, improvement in speech with a broadening vocabulary and improved engagement in conversations, more purposeful use of hands and
spk05: decreased
spk04: hand
spk05: wringing and staring. We also regularly hear feedback about the loved ones' increased cognitive ability or increased alertness,
spk04: with patients now being able to better follow conversations.
spk06: Caregivers
spk04: tell us they view these improvements as meaningful enhancements in quality of life for the patients in their care as well as their families. These testimonials all speak to the promise of treatment with debut and underscore exactly why we at Acadia do what we do to support and benefit those with greatest needs. Let's turn to slide 12 for a discussion of our New Plazaid franchise. I'll start by reiterating that our primary financial objective with New Plazaid is to optimize cash flow, and we do that in two ways. First, we're continuing to
spk05: grow by model shipments and marketing share in our eighth year on the market for PDP. The most effective lever to drive growth recently has been the broad educational campaign we launched last
spk04: year, bringing attention to our real-world evidence studies. These efforts have allowed us to grow new patient starts faster than the market. The second way we optimize New Plazaid franchise cash flow is by carefully managing expenses, and we'll continue to do that throughout 2024. These combined efforts have enabled us to generate over $300 million on a standalone, fully burdened basis in annual cash flow. Now let's turn to slide 13 to review our quarterly performance. In
spk05: the first quarter of 2024, New Plazaid
spk04: delivered $129.9 million in net product sales. As evidenced in the prescription data presented on this slide, the Parkinson's disease market remains largely flat, with both Carbidopa, Leodopa, TRXs essentially flat versus their prior quarter, while other antipsychotics and New Plazaid both increased by 4 and 6 percent respectively in the first quarter compared with the fourth quarter of last year. Importantly, New Plazaid outperformed growth in the PD market in both the office-based and long-term care channels. We're encouraged by these recent trends and look forward to continuing to grow this franchise. I'll now turn it over to Kimberly Manhard, Senior Vice President of
spk05: Global Strategic Planning and Execution.
spk09: Thank you, Brendan. In addition to our commercial products, we have a strong pipeline of late-stage clinical programs and early-stage disclosed and undisclosed programs, providing us with several opportunities to further expand our growth. Our review of our two late-stage programs. Please turn to slide 15 to discuss our ACPP-101 program, the treatment of hyperphasia, and Prader-Willi syndrome,
spk05: or PWS. Let me start with just a brief background on the disease. Prader-Willi
spk09: syndrome is a rare genetic neurobehavior disorder that affects approximately 8 to 10,000 patients in the US. The defining characteristic of PWS is hyperphasia, which commonly begins between the ages of 3 to 8. Hyperphasia is characterized by unrelenting hunger that often leads to obesity and behavioral challenges, such as
spk05: anxiety and aggression. As you can imagine, it is extremely distressing
spk09: for patients, as well as parents and caregivers of patients with PWS. To illustrate just how devastating this disorder is, the average life expectancy is 30 years, largely due
spk11: to obesity and resulting cardiovascular
spk05: related diseases.
spk09: Hyperhidrosis in PWS represents a significant unmet need, as there are currently no therapies approved to treat it. Let's now turn to slide 16, where we describe our clinical program in Prader-Willi syndrome.
spk05: Last year, we initiated
spk09: a phase 3 study of ACPA-101 for the treatment of hyperphasia in PWS. This study builds on the prior phase 3 experience and includes the .2-milligram dose that was shown to significantly reduce hyperphasia-related behaviors. As you see on this slide, the Compass PWS is our phase 3 global, multi-center, randomized, double-blind, 12-week placebo control study, evaluating the efficacy and safety of ACPA-101 in approximately 170 Prader-Willi patients. The primary efficacy endpoint is improvement of hyperphasia, as measured by the Hyperphasia Questionnaire for Clinical Trials, or H2CT scale, also used in the prior phase 3 study. Those patients who
spk05: complete this study are eligible to enroll in an open-ended,
spk09: long-term extension study. If data from the phase 3 study are positive, we plan to submit a new drug application for the treatment of hyperphasia in PWS to the FDA. The Prader-Willi community has incredibly high level of enthusiasm for this opportunity and interest in our study. We look forward to working with them and with clinical experts as we continue to advance this program. Please turn to slide 17 to review our second late-stage clinical program, ACP204. ACP204 is our next-generation 5-stage T2A compound that we're developing as a potential treatment for Alzheimer's disease psychosis. Similar to Pimavansren,
spk05: ACP204 works primarily in the -to-end
spk09: process of the first test of sadness at the 5-HT2A receptor. With ACP204, we are seeking to build on our learnings from Pimavansren and believe it is an exciting product opportunity. Our work completed to date includes a comprehensive phase 1 program that supports our target product profile for ACP204, including no sign of QT prolongation at planned doses in our studies, a wide dose range established, supporting the potential for dose equivalent to approximately two times the approved Pimavansren 34-milligram dose, and steady-state PK achieved in less than half the time of Pimavansren, suggesting potential for an earlier onset of activity.
spk05: ACP204's profile could represent a significant improvement over the already strong
spk09: product profile for Pimavansren. Please turn to slide 18. Our Seamless Phase 2, Phase 3 program for ACP204, which we have aligned on with the FDA, builds on our clinical experience with Pimavansren and is now underway. Our plan includes a phase 2 study with over 300 patients, which is designed to roll seamlessly into two phase 3 studies. This phase 2 study is ongoing and is designed and sized in such a way that if successful, it could be considered an adequate and well-controlled registrational trial. Once the full study allocation of patients for phase 2 is complete, we will analyze and
spk05: report
spk09: phase 2
spk05: results. By the time we know which time the two phase 3 studies will already be underway,
spk09: we are pleased to be advancing both of these promising late-stage clinical assets and look forward to providing future updates. And now I'll turn it over to Mark for a financial update beginning on slide 19. Thank
spk02: you, Clingerly. Let's review our quarterly financial performance on slide 20.
spk05: In the first quarter, we recorded $205.8 million in total revenue. That's up to 74% from the first quarter of last year. Today, the U.S. and the United States' net product sales were $75.9 million in the first quarter, which was
spk02: a sequential decline of 13% as compared to the fourth quarter of 2023. The sequential quarterly change was comprised of a 10% reduction in bottles sold and a 3% reduction in net price due to
spk05: higher
spk02: growths
spk05: to net. In terms of the reduction in bottles sold, on our last call, we described the seasonal dynamics that were affecting our business in the first quarter, including fewer rents and rent patient
spk02: visits, as well as reductions in refills and conversion rates due to the beginning of the year insurance reauthorization and re-enrollment process. In addition, for a period of time, numerical discontinuations outpaced new patient starts, the dynamics of which were described earlier by Steve and Brent. As we are now back to a period of net patient ads and the first quarter seasonal dynamics are behind us, we are confident in our ability to grow debut sales on a -by-quarter basis through the remainder of the year. New Placid net product sales were $129.9 million in Q1, up 10% versus the prior year's first quarter. Growth to net for New Placid was .1% in Q1. Our New Placid
spk05: franchise has achieved 44% demand bottle growth year
spk02: over year driven by increases in new patient starts in both segments. Sell-in growth increased by 6%, benefiting from the impact of a larger reduction in in-channel inventory in the first quarter of last year as compared to the level of in-channel inventory reduction we experienced in the first quarter of this year. R&D expenses decreased to $59.7 million in the first quarter of 2024 from $69.1 million in the first quarter of 2023. The decrease was mainly due to the Triphenotide commercial supply build in Q1 2023 that was accounted for as R&D expense as those expenditures took place prior to the FDA approval of day
spk05: two. We had a similar situation with the Q1, Q2, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q10, Q11, Q12, Q13, Q14, Q15, Q15, Q15, Q15, Q16, Q16, Q17,
spk02: Q17, Q18, Q19, Q20, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q21, Q 1-2023. Individuals從 ning包含一致國政府協議的大局面say an integral Us I transportation of debut expenses asже東西入�� sala video🚞 we dayview expenses as��🤡🤡🤡著 $3.56~!IS! $430.9 galaxies! Turning to slide 21, you can see that we
spk05: are reiterating our guidance for 2020-2024. And now I'll turn the call over to Steve for closing remarks. Thanks, Mark. Now please turn to slide 22. Looking to the end of the year and beyond, we are focused on penetrating the significant opportunities that remain in front of us for debut in the United States. Together with new compliance with the United States President, we expect our commercial franchises to drive strong growth. We are excited to bring debut to the markets outside of the U.S. and we are making strong progress already this year. We look forward to further enrolling
spk03: our two late-stage programs, including our Phase 3 program for Carter-Willi Syndrome and our seamless Phase 2 Phase 3 program in Alzheimer's disease psychosis. We're pleased to have these terrific opportunities ahead of us, while at the same time being in a position to generate sustainable and growing cash flow from operations to fund future growth. With that, I'll turn the call over to our Operator for Q&A. Operator?
spk13: Thank you so much. And as a reminder, press star 1
spk05: to get in the queue
spk13: and wait for your name to be announced. We ask that you please keep your questions to one. Please stand by while we compile the Q&A roster. Our first question is from Tess Romero with JPMorgan. Please proceed.
spk07: Hi. Good afternoon, guys. Thanks for taking our question. On the business development front, curious, you know, you've previously talked a lot about an interest in rare disease and neuro. So just curious, how would you characterize your appetite today here? And can you speak to the amount of capital you would ideally allocate to BD activities and the amount of risk you would be willing to take on in terms of stage? And then quick follow-up just on debut. We talked about net patient ads in each of the last
spk05: six weeks. We just wanted to confirm with the correct interpretation be that
spk07: you expect this to continue, such that you are comfortable to reiterate the guide today. Thanks, guys.
spk03: Thanks so much, Tess. I'll take
spk05: the BD
spk03: question and I'll ask Mark to comment on your debut question. So in terms of BD, nothing's changed. It continues to be a very important part of our strategy. We are – it's always a little bit difficult to predict the timing of transactions because a lot of things have to come together, obviously, but we continue to be very active on the BD front and
spk05: looking at what I would characterize as some really interesting opportunities. You know, it is – like it was a little bit difficult to
spk03: project exactly how much capital we would allocate to a single individual deal or deals because it's really kind of fact-dependent. But what I would say is we do see a – what I would characterize as a very interesting opportunity set. And we will execute on deals that we think are
spk19: additive and
spk03: obviously add value to our base.
spk05: I
spk03: think that was it on BD. Mark, you want to take the debut guidance question?
spk05: Yeah, on guidance, thanks for the question. And I think your interpretation is correct. We do expect to have net patients as we do expect. We do expect to have net patients as we do expect. We do expect to have net patients as continue in a positive direction going forward. And that supports the reiteration of our guidance. Yes, I just
spk03: want to confirm. Did you have a third question on DBA? I think I captured all of it. I want to make sure.
spk07: Yeah, thanks, Steve. Thanks, Mark. Just on kind of stage of asset on the BD side that you'd be contemplating, how early would you go versus something more late stage?
spk03: Yeah, no, thanks. I appreciate the question. Also very opportunity-dependent. I would say as an industry, we've worked through several years there where the
spk05: biggest challenge that we and other companies have
spk03: had to deal with is the deals.
spk05: We're
spk03: honestly the capital markets because things, you know, capital is readily available and that just made it more challenging or more expensive to do partnerships or acquisitions. It's a little bit different environment today, and I'm seeing a much more fertile environment for dealmaking. And so having said that, you know, historically, because it was very challenging in very robust capital markets, we and other companies tended to produce more, that environment
spk05: produces more early stage deals. I guess this is the way to say it. We have been at the top for early and late stage deals. I think the
spk03: sweet spot of our capability translates to more of a focus on pre-commercial assets, although we do from time to time look at products that are already commercialized. And so I would say there are no, we're agnostic more or less to the stage of development of assets. We have a strong balance sheet. We have strong capabilities.
spk05: We certainly would love to do more late stage assets. You know, Debut and ACP
spk03: 101 and Prada Wille are two examples of deals that we've done at the late stage. And,
spk05: you know, we certainly would be eager to do more, do more early stages. It's more a function of the kinds of opportunities that exist in the market. Thank you. Thank you.
spk13: One moment for
spk05: our next question, please.
spk13: And it comes from the line of reach to Farah with TVCat. Please proceed.
spk08: Hi, guys. Thanks for taking the question. I apologize for any background noise. Can you guys talk about, if you have this number, the percentage of diagnosed patients that have
spk05: started
spk08: Debut
spk05: at any time in the year? Given the 50% long-term for 50% does that mean that, since you have 25% market share, 50% of diagnosed patients have attempted to
spk08: start Debut? And can you speak a little to what you know about restart rates and the number of patients that have started Debut? And how the R&D management plan might affect that. Thank you.
spk05: Reto, I'm not sure we understood the full question, but I think Brent didn't think so. I think I did, Reto, and thanks for
spk04: both portions of the question. So the first is the percentage of patients diagnosed, patients that are on Debut. As Steve pointed out, a quarter of patients, so 25, actually a little north of 25% of patients are on Debut. That would, I would discuss that in terms of diagnosed patients, forgive me, are on Debut. We have initiated therapy on Debut. We have prescriptions, obviously, for more. As you know, we work them through the payer access process so that we would expect that we will, as we have said with conversion
spk05: rates, continue to get additional prescriptions
spk04: in. Your second question was around restart rates. We do see restarts of patients, and that happens for a variety of reasons. In some cases, a patient and family may have gone to a prescriber that is not necessarily a RET expert, but is close by. They may have started on the full dose and may not have had the best of experiences. That's one group that tends to come back, as they've heard a bit more about titration, as a potential strategy for starting. So we see that. We also see patients that have gone through significant medical procedures and honestly take a break and then come back to therapy. That often happens. And as we've discussed, because of our family access manager team, we have very, we stay very close.
spk05: We have a very close, in some cases, proximity to each of these families, offering
spk04: support, whether they have decided to initiate debut or in some cases, if they have decided at least to take
spk05: a temporary pause or to continue to do so. So we're just trying to keep them up to date on what we're seeing and opportunities to restart. Got it. On the first
spk08: question, I don't think it was perfectly clear on my part, but is the 25 percent the number, Is it a good chance to start on debut or is it a bigger number of the percentage of diagnosed patients that
spk05: have at one point started on debut, but may
spk08: not have remained due to long-term confines with it? Thank you.
spk03: Yeah, thanks for the clarification. It is the former. 25 percent of the 5,000 diagnosed patients, or as Brenda said, slightly more than 25 percent, have initiated therapy on debut. We do obviously have some of those that have discontinued, but 25 percent have started therapy.
spk05: Thank you. One moment for our next question, please. And as a reminder, we ask that you please keep your questions to one. Our next question is from Gregory Rensa with RBC Capital Markets. Please proceed. Markets, markets, markets. Please proceed. Yes, hey Steve and
spk16: team. Good afternoon. Congrats on the progress tonight. Thanks for taking much of the questions. Just when it comes to the new patient starts, the question is just really around the rate of that. I certainly appreciate the discontinuations in the bullets that you commented on and kind of thinking those up with the totals. I'm just curious to what extent did you think there would be some degree of predictability
spk06: or maybe some stability on
spk16: anticipating a more stable rate of new starts, especially as you think about broadening to beyond the centers of excellence. Thanks so much.
spk04: Yeah, thanks much for the question, Greg. Brendan? Yeah, thanks for the question, Greg. So in terms of new patient starts, as we described in the first quarter, it was slow in January but did begin to pick up in February, March, again in April. So as we discussed in our guidance range, we do anticipate continuing an upward increase in new patient starts. The two factors I would say that factor in most notably for us will be new patient starts and net patients. So as
spk05: we've also described, we've seen a number of
spk04: discontinuations, which we think is logical based on the bolus of patients that started and now a more consistent rate of patient adds week over week.
spk13: Thank you. One moment for our next question, please. Any questions from Amy Fadia with Needham & Company? Please proceed.
spk10: Hi, thanks for taking my question. You mentioned in your remarks that going forward you expect a significant portion of the growth to come from non-CUE high-volume centers as
spk11: far as community centers, which often tend to be more sort of spread out. How are you thinking about sort of the commercial effort in
spk05: educating and reaching these patients so
spk06: that
spk11: they can stop patients from therapy appropriately with the dietitian schedule that works and enable patients to stay on drugs longer?
spk03: Thanks much for the question, Amy. Brendan, you want to take that?
spk04: Yeah, sure. Thanks for the question. And maybe from my prepared comments, I would say that obviously in the early days we had a substantial number of patients come from centers of excellence, but we already had a good number of patients that were coming from those high-volume institutions, non-COEs, and from the community. And what I think we've seen is a very logical migration of where prescriptions are coming from. So,
spk05: you know, well over 50% coming from COEs in the early days, now more
spk04: like
spk05: a third
spk04: coming from COEs and two-thirds coming from the others. From there, I think we have a basis of experience in those two latter segments. What we're really focused on are the real-world benefits that have been seen for debut because I think the tangible conversations that take place with caregivers are more around what I'm going to see in my patient. What am I going to see in my loved one? So we've created vignettes that look at patients over the age of 20, teenagers as well as pre-teens and two- to -year-olds to give a much clearer perspective on what the treatment opportunity looks like and the benefits that they can expect to see in debut. And then I think embedded in the question was a question about our ability to get to these patients wherever they are. We have a great footprint to cover all of the retreaters and we also have claims data that helps us more deliberately track down those physicians that will be the point person either at a high-volume institution or the community for us to engage in those conversations.
spk13: Thank you. One moment for our next question. And it comes from Yatin Suneo with Guggenheim. Please proceed.
spk18: Hey guys, thank you for taking my question. Could you clarify what is gross to net right now? And then since you have reached 50% penetration in COEs, could you just comment on the level of penetration that you could reach in non-COEs over time and where you can push the COEs?
spk03: Thanks much for the question. Mark, you want to take the other question, Brendan? I presume
spk02: you mean the question on gross to net is related to debut. Yes. So I think for us, as we talked about in the last call, we're tracking towards 20% for the year and we don't expect that to fluctuate on a -by-quarter basis. So we're not going to disclose it as we go along. And I would just say maybe qualitatively in the first quarter we're just slightly below that target.
spk04: And for the second part of your question, I think in two parts. For COEs, with 50% patient penetration, I think we have tremendous momentum in these core areas of where these patients are treated. We'll continue to
spk05: work through that
spk04: population. I think that as you get further and further up the curve, obviously the engagement of those families with COEs is a critical factor for how far we'll get for penetration there. But we do see that in high-volume institutions and in the community, some of these conversations are easier for us to engage in in terms of our ability to get -to-face with those physicians to talk about the benefits that they see for debut. And then it's really a function of working very closely with them to make sure that they can get to their families, alert them that a therapy is available and get
spk05: them in for treatment. In terms of penetration, I think we expect to have similar rates of
spk04: – I think we expect to see rising rates of penetration in high-volume institutions more closely replicating what we see in COEs. And then in the community, it really depends on kind of the physician level of engagement that we're seeing and the proximity of the last kind of discussions they've had with their RET patients. But we're encouraged by what we're seeing early on.
spk13: Thank
spk05: you.
spk13: One more moment for our next question, please.
spk05: And this one is from
spk13: David Wong with City Group. Please proceed.
spk19: Hi there. Thanks for taking the question. I just wanted to ask about whether you had any insight on whether persistency differs between COEs and the non-COE community segment.
spk05: And how much room is there to improve? Thank you very much for the question, Brendan. You want to take the question? Yeah. Yeah, sure, David. Thanks for the question. Yeah, sure. Sure, David. Thanks for the question. At the top of the
spk04: top, I'll say that there are not wide disparities in persistency rates between COEs and non-COEs. What I think we see is more the proximity to the patient and the work done on a GI management strategy so that there's a clear discussion upfront with the families
spk05: about the treatment during the end of the year. And then there's the options that are available to make sure they manage that. So the more experience... ...the more consistent I think their approach to GI management becomes, the better persistency. Yeah, so I think it's more... ...a function of that than it is whether you're in a COE or not.
spk13: Thank you. One moment for our next question. And it's from the line of Joel Beatty with Baird. Please proceed.
spk20: Thanks for taking the question. For the numerical discontinuations in the first six weeks of the year or so, could you characterize those a little bit more, such as what was the cause and was it driven more by lower patient starts during that time or higher than usual discontinuations?
spk03: Thanks much for the question, Joel. Brendan, do you want to take that?
spk04: Yeah, Joel, thanks for the question. Numerical discontinuations were largely what we would expect, which is why we reiterated the point around the consistency of our persistency curve. We do think from a seasonal perspective, there were some patients that
spk05: started perhaps in the fourth quarter that continued early. It may not have been an appropriate timing for them to have started to give you a run around the holidays,
spk04: for example. That may have contributed from a seasonal perspective to slightly higher numerical discontinuations than anticipated.
spk05: Thanks. Thank you. We'll take a moment for our next question. And it's from the line of Jeffrey Hong
spk13: with Morgan Stanley.
spk05: Please
spk13: proceed.
spk01: Hi, good afternoon. This is Kathy Fernand for Jess. Thank you so much for taking our question. Just another one on the Centers of Excellence from us. Now that we're a year into launch, have you observed
spk05: COEs increasing the number of threat clinic days from
spk01: the once monthly you mentioned last quarter to a more frequent basis? And do you have an updated average number here?
spk05: Thanks so much for the question. And Brendan?
spk04: Sure. Thanks for the question. In most cases, I would say that COEs are maintaining the process that they've had to engage families. There are a handful of centers that have increased COE days, increased threat clinic days. There are a couple that have specific debut clinic days as well. But generally, I would say it's been consistent with how they've seen patients over time.
spk05: Okay. Thank you. One more moment for our next question, please.
spk13: And it is from the line of Charles Duncan with Cancer. Please proceed.
spk12: Hi, this is Elaine for Charles. Thank you for taking our questions. I just wanted to ask, I think at the last update you said that the age range was
spk05: comparable or spread throughout the year. For debut,
spk12: would you say that the key drivers for demand such as real-world benefit and establishing GI management, strategies, does it depend per age range?
spk04: Thanks so much for the question. Brendan? Yeah, sure. Thanks so much for the question, Elaine. I would say that we're still seeing largely what we expected in terms of the existing prevalent population for RET, meaning
spk05: that we're
spk06: getting the
spk05: age
spk04: range and
spk05: the
spk04: respective weights that we would expect to see in terms of a patient mix. If anything, in the first part of 2024, we've seen slightly older and heavier patients that have been started on debut in terms of the patient mix, which might lead to somewhat of an increase in average dose as a function of that.
spk12: Thank you.
spk13: Thank you. One moment for our next question, please. And it's from the line of Jason Butler with SIP Distance, JMP.
spk19: Good
spk05: afternoon. This is Joseph for Jason. Thanks for taking our questions. How do you think about the potential role of GMC therapy to see RET syndrome and how could debut be used alongside it? I think it's a pretty early development, but we're just curious about your thoughts. Thank you. Yeah,
spk03: thanks much for the question. I'll start by saying we hope that debut is the first of multiple drugs approved to treat this highly debilitating disorder. As it relates to gene therapy, I think that we know that gene therapy can be very challenging. We've even seen some of the challenges played out just in the last week with gene therapy generally speaking. In RET, it's a little bit more of an additional hurdle here because with RET, there's
spk05: kind of a Goldilocks level of expression that you want to operate
spk03: with them because if you have too much expression, you get the same symptoms, you give them too little. And so there are a couple of companies that are in very early stages of testing on gene therapy, and I think there's just a lot more to come. It won't be rapid. Nothing is in this industry. It will take some time, but we're certainly hopeful that there will be, again,
spk05: that debut will be the first of many therapies for this population. Having said that, if we think about additional drugs becoming available, including gene therapy, we don't see any reason that debut
spk03: couldn't be prescribed alongside other drugs as well. And so these
spk05: patients are so highly symptomatic that if you had another therapy,
spk03: gene therapy or otherwise, that reduced symptoms by 50% or even 75%, they would still be highly, highly symptomatic and in need of therapy. And so we believe that we should be envisioning
spk05: a debut operating in a world where
spk03: if there are
spk05: other
spk03: therapies down the road, we believe that it would be very compatible with those therapies and have the potential to provide additive benefit.
spk19: Very helpful. Thank you.
spk13: Thank you. One moment for our next question, please. And it's from Ash Verma with UBS. Please proceed.
spk17: Hi. Thanks for the question. I had to. So for debut, I know in prior instances you have actually offered the sales for subsequent quarters. This time, I don't think you just left it at sequential growth. Is there any reason
spk05: for that? If anything, you sound very optimistic. Contrainduct on
spk17: the rebounds is a serious sort of driving that dynamic. And then secondly, I wanted to ask about your cost structure. Like, have you considered revisiting that? I mean, compared to last year, this year we've seen nucleoside negative symptoms not working out favorably. And the debut persistency coming in below, I'm guessing that you would have originally assumed. Does that make you rethink where your cost structure is? Thanks.
spk03: Yeah, Mark. Thanks much, Ash, for the questions. Mark, I'll let you take both of them.
spk02: Yeah, sure. Sure. On the guidance, as we transition to annual
spk05: guidance, I'm just going to start out with your notes. I don't know how long it is. I'm just going to give the kind of -on-one code forward, one quarter forward guidance. And then I guess you need to think about the first quarter or this year. So, the first quarter guidance for this year, the first quarter guidance for this year, is that we were expecting a sequential down order. So, we thought that was just helpful in
spk02: giving the full financial expectations for the year to give the first quarter guidance for this year as well as annual guidance. We don't expect to see sequential declines going forward, so we're going to keep the annual guidance just like we do for New Placid. On the cost structure, thanks for the question. As Chief Financial Officer, of course I look at the cost structure
spk05: every day. But I think
spk02: as we look at what was the right cost structure for the business and the investments that we're making, there's no change there. Yes, we had our, unfortunately, our negative symptoms of schizophrenia trial was not possible. We had made
spk05: investments in commercial investments in negative symptoms of schizophrenia trial. But before that, we read out the analysis. So, there really is nothing to unwind. Our business is expanding. We're making investments for ex-US. We're making investments for the first debut that didn't exist last year. So, that's kind of a new leg
spk02: to the business that requires investment. And we're still investing appropriately for growth and debut in the US. So, all of that together leads us to supporting the investments that we're making. But as we've done the last couple of years in New Placid, we've looked at that franchise of making efficiencies. And we look to make the right investments as additional investments or reduction investments across our entire cost structure on an ongoing basis.
spk13: Thank you. One moment for our next question, please. And
spk05: it comes from the line of Mark Goodman with Lilly Hearing. Yes, my question is around
spk21: the Prader-Willi trial. I'm curious if GLIP-1 uptake has been hindering enrollment and just the general thoughts around how GLIP-1s will play into potentially not needing as much therapy for Prader-Willi and the eating disorder there. And then secondly, can you just give us a sense of how many patients are on New Placid these days? We haven't talked about it yet. Thanks.
spk03: Thanks much, Mark, for the question. I'll take the first one. So, in Prader-Willi, we've seen no impact at all of GLIP-1 utilization. In fact, as Kimberly mentioned, we have a very enthusiastic patient population
spk05: and medical community.
spk03: And enrollment is moving very well. We're enrolling ahead of plans. So we haven't seen any impact of GLIP-1 or anything else, honestly. I'm sorry. Second question, Brendan, you want to take that on New Placid?
spk04: Yes, sure. Thanks for the question, Mark. We're continuing to see increases in patients on therapy on a quarterly basis. So between the community and LTC in long-term care, obviously we have great visibility into the community. And so we've added patients in the first quarter or over the fourth quarter on the order of about 8,500 in total patients. And then in LTC, that's obviously more like a quarter of our business. But you know
spk05: that prescriptions are often split between the community and patients. So we don't have absolute visibility into
spk04: the number in long-term care.
spk13: Thank you. One moment for our next question, please. And he's from Sumant Kulkarni with Kanna Korjianuiti. Please proceed.
spk15: Good afternoon. Thanks for taking our question. On debut discontinuations, is there a sweet spot in terms of months on drugs where discontinuations tend to cluster, and if a patient remains on drugs after that, they tend to do so more easily after they pass that point? And are most discontinuations confirmed by clinical visits or are they patients that have gone greater than 60 days without a refill?
spk03: Thanks much. I'll answer the first part. Brendan, I'll ask you to answer the second part in terms of the split on
spk05: discontinuations.
spk03: So, Sumant, we do see, we touched on this on the call, so let me just expand on it a little bit. We do see more discontinuations in the first two fills of drugs, so there's a disproportionate number of discontinuations there. Now, some of that you would expect. We see this pretty routinely with drugs that have subjective endpoints. We see it all the time in neuropsychiatry where you have a steeper level of discontinuations in the first two to three months. So we do see some of that. We do feel, however, though, as we parse through that data, that given the level of titration that we're seeing across the brand and just recognizing that it takes longer than to get to therapeutic levels, that we do think that some patients are discontinuing prematurely before they have an opportunity to see those benefits.
spk05: And
spk03: there's an opportunity
spk05: for us there to improve on that. And it's a high area of focus for us to now, and it's a broad area of focus, and we just discussed on the call, particularly on educating caregivers and medical professionals around their
spk03: expectations around time, setting the right expectations about time to get the benefits, and then managing to that is a very important area of focus for us. Brendan, do you want to take the
spk04: other
spk03: question?
spk04: Yeah. So Steve obviously did a great job of kind of articulating where we are with
spk05: when discontinuations take place. And it's probably intuitive,
spk04: but the further out we get in fills, the flatter the
spk05: curve gets, right? There are fewer and fewer
spk06: patients that are discontinuing when
spk04: you get beyond four and five fills with debut. And I think we're encouraged by that on two levels. Number one is obviously our fans are very close with these families. We have weekly conversations with them, so we have good confidence that once they get through that early part of that period, patient journey and tolerability, GI management strategies, we do a nice job of keeping them on therapy. And we also know from talking to centers of excellence how often they're seeing these patients. Many of the physicians want to see their patients regularly after they start. The vast majority of them, I think, want to see patients at the month three time period, partially because that's the length of the clinical trial, partially because some payers are
spk05: asking for that information. And then
spk04: I think they make judgment calls on how well the patient is doing, how often they want to see them after that. But with persistency rates now out to nine months in what we're seeing, I think we feel confident in what we're seeing in terms of patients being able to start and stay on therapy after they get through the early part of the treatment journey.
spk13: Thank you.
spk02: I think I'll just add one thing to that. I think the question was also, are more discontinuations happened because they're confirmed versus going over 60 days? And I think you asked it in the context of is it a clinical decision? I think for us with the connectivity we have with our FAMs, we do find for the data we receive, the majority of discontinuations are confirmed discontinuations, and it's the minority of discontinuations that are
spk05: being discontinued for greater than 60 days,
spk02: many of which of those subsequently become confirmed when spoken to the caregiver. Thanks for that clarification,
spk13: Mark. Thank you. And we have one moment for one more question. One moment, please. Any questions on the line of OUI-AIR with MSUHO? Please proceed.
spk14: Hey, guys. Thanks for including me. Yeah, just some question on New Plastic. So you indicated that, you know, real evidence has sort of grown on New Plastic. I'm just wondering,
spk20: like, is
spk14: it, what exactly is it? Is there anything that's kind of like, that's changed in
spk05: practice
spk14: or
spk05: patients, I
spk14: don't know, less scared to come back into the office? The physicians office, or is there anything fundamentally in the physicians office in the long-term care that is perhaps increasing the number of patients? And secondly, would you consider perhaps increasing your investment
spk05: to
spk14: drive further
spk05: growth?
spk14: Thanks.
spk05: Thanks much for the question, Brittany. You want to take the first question? For sure. So I think there are
spk04: a couple of dynamics. If you'll recall, Carbidopa-Levodopa scripts in the peak of the pandemic and even towards the end were declining over time. And declining would suggest fewer Parkinson's disease patients overall. Even today, we'd say that's flat. So I wouldn't call that a rebound by any stretch of the imagination. I would call that stability. But I think also easing safety measures that have patients returning to clinics and hospitals are certainly giving us more shots on goal for New Plastic as the choice for PDP. I think that, combined with real-world evidence, has given us a very compelling story on why we should be the first and best choice and has given us an opportunity to grow share. And what we've seen in long-term care, I think, has been pretty logical in terms of resident counts in long-term care facilities. They obviously plummeted during the pandemic. Towards the latter part, they have increased. They have continued to increase, but New Plastic's performance has outpaced both the resident counts and APs in that space.
spk03: I'll take the second part of that. So as Brynnen mentioned, when we look at metrics like Carbidopa-Levodopa, it looks like the overall PDP market is relatively steady or flat. But we are seeing growth with New Plastic there. And I think that's the genesis of your question. So would we consider increasing our investment? And I think the answer is we do monitor that, too, on a -to-day, -to-week basis. We look for opportunity. We're constantly assessing is this the right level of investment given the opportunity? And as we've said before, if we feel like there's opportunities to produce
spk05: an appropriate ROI, we may make those investments. But I think that's just
spk03: a key element of our overall objective of optimizing cash flow.
spk13: Thank you. And with that, I will conclude a Q&A session and pass it back to Steve Davis for final comments.
spk03: Thank you, operator. Thanks again, everyone, for joining us today. We look forward to updating you on our progress next quarter.
spk13: And with that, we thank you all for participating, and you may now disconnect.
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