Q2 2025 Alkermes PLC Earnings Call

Please.

If you should require operator assistance during the call. Please press star zero from your telephone keypad.

Please note that this conference is being recorded.

I'll now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and corporate Affairs.

Sandy you may now begin.

Good morning, welcome to the Alkermes plc conference call to discuss our financial results and business update for the quarter ended June 30 of 2025 with me today are Richard Pops, Our CEO Blair Jackson, our Chief operating Officer, Todd Nichols, Our Chief Commercial officer, Dr. Craig Hopkinson, our Chief Medical officer and darker Dr.

Market Young Vice President of clinical development, a slide presentation, along with our press release related financial tables, and reconciliation of the GAAP to non-GAAP financial measures that we'll discuss today are available on the investors section of Alkermes Dot Com, we believe the non-GAAP financial results in conjunction with the GAAP results are useful in understanding the ongoing.

Mix of our business our.

Our discussions during this conference call will include forward looking statements actual results could differ materially from these forward looking statements. Please see slide two of the accompanying presentation. Our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those.

Breast or implied in the forward looking statements, we undertake no obligation to update or revise the information provided on this call or in the accompanying presentation. As a result of new information or future results or development. After our prepared remarks, we'll open the call for Q&A and I'll turn the call over to Richard for some opening remarks.

Thank you Sandy and good morning, everyone. We had a very successful second quarter, our commercial and financial performance was strong and last week. We took another major step forward in our pursuit of a medicine that has the potential to transform the treatment of narcolepsy.

Now midway through 2025, we're on track to deliver on our key objectives across the business and commercial we had plan for strong sequential growth and we exceeded our expectations in the second quarter.

This result was driven by excellent operational execution by a seasoned commercial team.

With sustained profitability now no debt and more than $1 billion of cash.

We're in a strong financial position with significant optionality.

It's clear to us now that the future growth of the business can be accelerated by the development candidates now in our pipeline.

Last week, we reported positive topline results from Vibrance. One this was our first phase II study of <unk>, which you formerly known as <unk> 2680 in narcolepsy type one.

Vibrance one was successful in a critical study in the development of our <unk> portfolio, obviously for the efficacy and safety data in yields but also for the operational foundation. It provides for the phase III program.

Now if you think back a year ago, we had data from our phase <unk> study of Elixir Exton that suggested the robust efficacy and a generally well tolerated profile based on single they exploded exposures across a range of doses in small cohorts of patients with narcolepsy type one narcolepsy type two and idiopathic hypersomnia.

These data were critical and defining the initial clinical profile and dosing range for <unk>. This was step one step two is to confirm and extend these observations in multi week multi dose phase two outpatient studies vibrance one in patients with narcolepsy type one is the first of these studies now.

Now we have randomized placebo controlled six weeks multi dose data in hand for more for more than 90 patients within tier one.

We've now answered key questions in phase two with rigorous assays across larger cohorts of <unk> patients over a longer period of time. These data and insights will be fundamental in preparation for phase III.

So here the key findings from this study at the top line first the results demonstrated a significant effect on wakefulness and a generally well tolerated profile. This was our pretest hypothesis and the data were in line with our expectations.

The study provided an entirely new and exciting findings relating to fatigue in cognition. These are among the most disruptive symptoms patients with narcolepsy experience and they are distinct from excessive daytime sleepiness.

In this study <unk> showed robust and clear improvements on validated patient reported measures.

Our view is that demonstrating effects in these domains establishes a new standard in the development of Rexam two receptor agonist and narcolepsy.

These emerging data also further support our hypothesis that the orexin system can be harnessed to address other neuropsychiatric and neurological conditions. We have two additional orexin candidates, we plan to develop for conditions beyond central order disorders of Hypersound noise. In Q2, we initiated first in human studies for one of these candidates.

Alex 45 10.

We plan to advance the second candidate out 70 290 into the clinic later this year.

So for today, Craig and Marcus will take you through the topline results of Vibrance, one with significantly more detailed data to be presented at the upcoming world sleep meeting in September, but first Blair and Todd will review the financial and commercial performance of the business for the second quarter and with that I'll hand, the call over to Blair. Thank.

Thank you rich our second quarter financial results were strong and reflected solid commercial and operational execution. We had planned for accelerated growth from the first quarter and we exceeded our expectations financially. The year is progressing nicely and we remain well positioned to achieve our financial guidance for the full year, which we reiterated this morning.

For the second quarter, we generated total revenues of $397 million.

For our portfolio of proprietary products, we generated net sales of $307 $2 million, reflecting 14% year over year growth.

These results were driven by strong underlying demand, which Todd will address in his remarks and gross to net favorability primarily related to Medicaid utilization rates and certain other credits during the quarter.

These factors drove a one time gross to net benefit of approximately $9 million for <unk> and approximately $11 million for aerostar taken together. These gross to net dynamics resulted in our proprietary product revenue tailwind of approximately $20 million in Q2.

As we move into the third quarter, we expect Q3 net sales from this portfolio in the range of $280 million to $300 million.

Manufacturing and royalty revenues were $83 $4 million for the second quarter, including revenues of $39 $4 million from <unk> and $33 million from the long acting and Vega products.

Turning to expenses cost of goods sold were $49 5 million.

Which compared favorably to $61 5 million for Q2 last year, primarily reflecting efficiencies following the sale of our Athlone based manufacturing business last year.

R&D expenses were $77 4 million compared.

Compared to $59 6 million for Q2 last year, reflecting investments in the vibrant phase two studies of elixir accident across narcolepsy idiopathic hypersomnia.

We expect R&D expense to step up slightly in the second half of the year as we complete our phase II studies in narcolepsy and continue to build momentum in our phase two study in idiopathic hypersomnia.

SG&A expenses were $178 million compared to $168 1 million for Q2 last year for.

For trending purposes, we expect SG&A expense to be fairly consistent in Q3, and a modest decrease in the fourth quarter of the year.

This performance generated strong profitability of GAAP net income of $87 1 million EBITDA of $101 6 million and adjusted EBITDA of $126 5 million in the second quarter.

Turning to our balance sheet, we ended the quarter in a strong financial position with one $5 billion in cash and total investments. We continue to have $200 million of remaining share repurchase authorization and going forward, we may opportunistically repurchase shares depending on market conditions and the capital needs of the business.

<unk>.

As we look ahead based on our performance during the first half of the year and the expected contribution from our expanded sales efforts. We're on track to deliver record revenues from our portfolio of proprietary products in 2025.

As a result of this strong performance, we now anticipate finishing the year towards the higher end of our previously issued financial expectations in terms of both revenue and profitability.

With that I'll turn the call to Todd for a review of the proprietary portfolio.

Thank you Blair and good morning, everyone in the second quarter, we recorded net sales from our proprietary product portfolio of $307 2 million.

Reflecting 14% year over year growth, we drove strong end market demand across Vivek troll, Aerostar, and Lee ball vision by executing targeted growth initiatives and delivered strong sequential growth from Q1 to Q2.

Due to this demand growth and the gross to net favorability during the quarter that Blair outlined.

Our second quarter proprietary net sales.

A $307 $2 million exceeded the expectations that we provided in may of.

Net sales in the range of $260 million to $280 million.

Starting with <unk> net sales in the second quarter were $121 $7 million.

<unk> performance continues to be driven by growth in the alcohol dependence indication market and our ability to capitalize on highly localized market dynamics.

In certain states and payer systems looks.

Looking ahead, we continue to expect <unk> net sales for the full year 2025, and the range of $440 million to $460 million.

Turning to our psychiatry franchise.

The expansion of our psychiatry sales force completed earlier. This year was an important element of our strategy to maintain a competitive share of voice <unk> and reaccelerate growth for aerostar. The early returns from that expansion are encouraging and we are pleased with our progress to date.

Are there startup product family in the second quarter net sales were $101 3 million.

Leading indicators related to underlying demand were encouraging with increased prescriber breadth and strong new to brand prescriptions during the quarter for the full year 2025, we continue expect aerostar net sales in the range of 335% to $355 million.

Turning to <unk> net sales grew 18% year over year to $84 $3 million.

<unk> growth was 22% year over year, driven by new patient starts and prescriber breadth gross to net adjustments were approximately 29% in the second quarter. We now expect gross to net adjustments for the full year will be approximately 30% for.

For the full year, we continue to expect <unk> net sales in the range of $320 million to $340 million.

Across the portfolio. We are pleased with our second quarter performance and are focused on maintaining this momentum and driving demand in the second half of the year with that I will pass the call to Craig.

Thank you Todd last week, we announced positive topline results from the Vibrance, one phase II study of <unk> in patients with narcolepsy top one.

The data further characterize the clinical profile of <unk> and demonstrated that once daily elixir Exton normalized wakefulness of excessive daytime sleepiness scholes in highly symptomatic patients with narcolepsy type one with a generally well tolerated profile across all doses tested.

These topline results represent the first of a series of datasets that will emerge from the <unk> phase II program.

The data are extensive and break new ground.

We're looking forward to presenting the primary and key secondary endpoints related to wakefulness in cataplexy and the safety and Tolerability profile observed in the six week double blind period of the study and an oral presentation at the upcoming World sleep meeting at the beginning of September.

In addition to the topline results. We will also share data relating to the exploratory patient reported outcomes collected in <unk>, one, including the fatigue and good condition data outlined in our topline press release last week.

These data are truly exciting not only in terms of the clinical profile of <unk>, but also as we plan for additional clinical studies across our portfolio of invest investigational orexin two receptor agonists in disorders, where impaired cognitive functioning and fatigue, a key clinical features.

Following world Sleep, we expect topline results from <unk>, two a phase II study in narcolepsy top two in the fall.

Enrollment in <unk>, two is going well and we expect to complete that soon.

Topline data from <unk> three a phase II study in idiopathic hypersomnia are expected to follow in mid 2026.

Each of these studies provides us significant amount of data to analyze and we will deepen our understanding of elixir rates those potential utility across central disorders of Hopper somnolence and its differentiating features features and competitive in the competitive landscape.

In parallel we are preparing for key regulatory interactions and for the global Phase III program in narcolepsy that we plan to initiate it as rapidly as possible, calling the topline data from the narcolepsy top II study.

Alkermes is at the forefront of developments in this exciting potential therapeutic category and the positive <unk> data represents an important stride forward for elixir external development program and our broader portfolio of Orexin two receptor agonist.

With that I'd like to introduce Dr. <unk> to review the topline data from the <unk> one study.

Marcus as Vice President of clinical development and the clinical program lead for <unk> to Alkermes Marcus.

Thank you Craig Vibrance, one is a six week double blind placebo controlled parallel design study evaluating three different doses of <unk> in patients with narcolepsy type one or <unk> one.

The study enrolled a total of 92 patients with most having moderate to severe disease at baseline.

Patients were randomized to one of three once daily dose levels of <unk> for six or eight milligrams or placebo.

The primary endpoint of Vibrance, one was the change from baseline compared to placebo and the maintenance of wakefulness test or M. WT <unk>.

<unk> is a standardized quantitative measure of how long patients can stay awake during a 40 minute test period. When they are in an environment that is conducive to sleep.

These tests are conducted at 246 and eight hours post dose the.

The mean score is calculated by averaging the results of these four tests.

While the <unk> is less frequently used in real world clinical settings. It is an important objective endpoint commonly used for regulatory purposes.

And vibrant Swan Elixir Exton showed dose dependent statistically significant and clinically meaningful increases in mean sleep latency at all doses tested at week six.

Importantly, all dose groups achieved normative wakefulness applying the standard convention of amines sleep latency on the <unk> of 20 minutes or more.

The study also evaluated key secondary endpoints, including change from baseline on the Epworth sleepiness scale and weekly cataplexy rates compared to placebo.

First the epworth sleepiness scale or SaaS.

Unlike the MW T. This scale is widely used in the clinic as a diagnostic tool to assess for excessive daytime sleepiness.

The ESF as a patient reported symptom questionnaire asking about the patient's likelihood of falling asleep across eight different scenarios, such as watching TV riding in a car or reading a book over the last week.

Higher scores indicate a greater likelihood of falling asleep with a score of 10 and below considered normal.

The Epworth scale is useful and that the seven day look back period provides a holistic view of patient's sleepiness beyond the eight hour SWT test period.

Here across all doses tested elixir exton demonstrated statistically significant and clinically meaningful improvement at week six with each dose group achieving normative levels.

In addition to excessive daytime sleepiness and <unk> patients can experience, a sudden and voluntary loss of muscle tone called cataplexy.

<unk> evaluated mean weekly cataplexy rates.

It's a measure of this endpoint patients are asked to keep diaries of cataplexy events that they experience.

The average number of weekly events across weeks five and six in the <unk> treated subjects were then compared to those experienced by the placebo group.

Across all doses tested elixir exton showed numerical and clinically meaningful improvements in cataplexy compared with placebo.

And on the pre specified analysis met the threshold for statistical significance at the six milligram dose.

We are confident in the effects of elixir accident on cataplexy and believe there are learnings here related to our implementation of this assay that we will apply in phase III, so reduce variability and the impact of outliers.

We look forward to sharing additional analysis of these data at world sleep.

So while excessive daytime sleepiness is the hallmark symptom of narcolepsy. Many patients also experience other symptoms such as fatigue and cognitive dysfunction. These.

These can result in significant morbidity as well as impaired quality of life.

Our hypothesis has been given the nature of the neurosurgery affected that elixir Exton could have an impact on many of the aspects of this disease that affect patients' day to day functioning.

The British Columbia, cognitive complaints inventory or BC, CCI and the promised fatigue scales captured two of these common and often debilitating effects of narcolepsy.

The BC CCI evaluates concentration memory expressing thoughts work, finding slow thinking and difficulty solving problems. The promised fatigue measures patients frequency as well as intensity of fatigue, along with its impact on physical mental and social activities.

It is important to note here that fatigue is a symptom that patients experience, which is distinct from sleepiness.

While sleepiness is a general feeling of being tired and wanting to sleep fatigue is a broader feeling of exhaustion that can be long lasting and may not be resolved by sleep.

We also looked at the narcolepsy severity scale.

The NSS captures a holistic assessment of disease buyer.

By evaluating five key narcolepsy symptoms excessive daytime sleepiness, cataplexy hallucinations sleep paralysis and disturbed nighttime sleep.

And on each of these exploratory patient reported outcome scales. The BCCI the promised fatigue and the NSS elixir Exton demonstrated clinically meaningful improvements from baseline compared to placebo that were statistically significant.

Of course, the P values here are nominal due to the exploratory nature of these endpoints.

So from a clinical perspective. These results are compelling due to the robustness and particularly the consistency across all doses of <unk> as well as across various complementary assays.

This is the first time that we've seen data from the Orexin class on these fatigue and cognition scales and we believe this differentiates <unk> from other development programs and builds upon the evidence base that orexin two receptor agonists with appropriate pharmaceutical properties could have broad potential utility across a range.

<unk> of neurological or neuropsychiatric disorders.

And now I'll turn to safety and Tolerability overall elixir Exton was generally well tolerated in this study the majority of the treatment emergent adverse events were mild to moderate in severity and no treatment emergent serious adverse events, we're seeing.

The <unk> that did occur were generally consistent with the events that we observed across the phase one studies in healthy volunteers and in subjects with in tier one and tier two NIH.

And among the many clinical safety assessments, we conducted in the study to a particular interest our hepatic labs and ophthalmic exams and importantly, there were no treatment emergent safety signals seen in these assessments. So overall, we are very pleased with the safety and efficacy profile, thus far and we look forward to presenting these data.

The sets at World Sleep, I'll hand, it back to you rich.

Thank you Markus so that's a summary of the top line findings there is a lot more to come and you'll begin to see it in a few weeks at world sleep. These.

These data and <unk> represent a meaningful step forward for <unk> and development program and they provide a substantial new dataset that significantly expands our understanding of Orexin biology, not just relevant to narcolepsy, but has potential across a broad range of neuropsychiatric and neurological disorders.

We're now moving forward with confidence and a sense of urgency as we prepare for the initiation of our Registrational program in narcolepsy and.

And with clear findings now relating to cognition and fatigue, adding to what we've seen for excessive daytime sleepiness. We now have further data supporting development of additional rexon candidates in other disease states beyond sleep disorders as.

As you've heard throughout this call the business is in a strong position our commercial team is on track to deliver proprietary product net sales in excess of $1 billion.

And robust profitability in 2025.

Our balance sheet is strong and provides strategic optionality with more than $1 billion in cash our pipeline products are advancing <unk> as the first major potential commercial opportunity to emerge from our <unk> portfolio, but we also believe that sleep disorders are just the beginning for this exciting new therapeutic category.

Thank you for your patience with that I'll turn the call back to Sandy to run the Q&A.

Great. Thanks, Rob.

Rob we'll now open the call for Q&A. Please.

Thank you Sandy.

Conducting a question and answer session.

The last one any analysts to ask questions as possible. We ask you. Please limit yourself to one question.

If you'd like to ask a question at this time you May press star one on your telephone keypad and a confirmation tone will indicate your line is in the question queue.

You May press star two if you'd like to withdraw your question from the queue.

For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star.

Thank you and our first question today comes from the line of Paul Matteis with Stifel. Please proceed with your question.

Hey, good morning. Thanks, so much for taking my question and congratulations on all the progress I don't want to front run the World fleet presentation and ask a specific data question, but taking a step back theres been a lot of focus right or wrong from wall Street on visual adverse events with the Orexin program and I guess I wanted to ask the alkermes.

Team one do you think the focus on visual Aes is warranted.

Are we on the right track and kind of thinking about whether this is clinically significant and then two where would you draw. The line on visual a signal that is benign and might not have much regulatory commercial consequence versus something that might be more significant.

Require certain things like driving studies or could result in certain restrictions on our drug label. Thanks, So much.

Good morning, Paul Hey, let me start and then I'll hand, it over to the to the experts, but I can just tell you in my experience doing both with clinicians and investigators and patient groups and dealing with Wall Street. The focus is almost entirely on the wall Street side on the on the visuals.

And it's.

It's an important contribution that we made in this particular study because as I've said before there was a reasonable scientific medical question at the beginning of this program about weather Orexin two receptor agonist can have a direct effect on the high so with this rigorous baseline of sound like exam.

At baseline and then six weeks later, having 90 plus patients worth of data to established now that we saw no changes was an important step forward in that but I think from a clinical perspective I'll, let I'll. Let these guys comment on that and what their experience has been but we won't provide any more specific AE data on this call other than what's in the press release, but I think he can give you some qualitative sense of it.

Yes exactly.

As rich pointed out we're not providing additional <unk> data, but I think in general we do feel that based on some of our discussions that NDA.

That's thought to be mild and not interfering with patient's daily activity is not going to be something thats going to be overly concerning both for physicians or or for their patients.

Unknown Executive: All participant lines will be placed on mute to prevent background noise. If you should require operator assistance during the call, please press star zero from your telephone keypad. Please note that this conference is being recorded.

Baseline of found like exam.

Yes, maybe just to add to that we had a data safety monitoring board in place.

And then six weeks later, having 90 plus patients worth of data to establish now that we saw no changes was an important step forward in that but I think from a clinical perspective I'll, let I'll. Let these guys comment on that and what their experience has been but we won't provide any more specific AE data on this call other than what's in the press release, but I think he can give you some qualitative sense of them.

Seeing all safety from the <unk> program and made a number a number of times and given us the greenlight to proceed.

Sandra Coombs: I'll now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and Corporate Affairs. Sandy, you may now begin.

<unk> to that as Richard pointed out.

Richard Pops: Morning, welcome to the Alkermes PLC conference call to discuss our financial results and business update for the quarter ended June 30, 2020.

The logic exams with noble we established baseline.

[noise], yeah, exactly as rich pointed out we're not providing additional data, but I think in general we do feel that.

So that gives us some confidence there as well and then sort of Directionally as we said as we sort of said in our disclosure.

Richard Pops: With me today are Richard Pops, our CEO, Blair Jackson, our Chief Operating Officer, Todd Nichols, our Chief Commercial Officer, Dr. Craig Hopkinson, our Chief Medical Officer, and Dr. Marcus Yance, Vice President of Clinical Devices. A slide presentation along with our press release, related financial tables, and reconciliations of the GAAP to non-GAAP financial measures that we'll discuss today are available on the Investors section of Alkermes.com. Our discussions during this conference call will include forward-looking statements. Actual results could differ materially from these forward-looking statements. Please see slide 2 of the accompanying presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements.

Adverse event profile is in line with what we saw across the phase one healthy volunteer and patient cohorts from the Phase One program Hey, Paul Let me just add because it might anticipate some other questions. We're going to get just as a matter of fact, the safety database is actually not even closed until probably mid August because recall, we have a seven week extension that fault.

Based on some of our discussions that any AE.

Thought to be mild and not interfering with patient's daily activity is not going to be something that's going to be overly concerning both for physicians or or for their patients.

Yes, maybe just to add to that we have.

That is after monitoring board in place.

Is the six week double blind, so actually we couldnt populate data tables with specific numbers until that database is locked so part of the reason for the level of disclosure at the at the.

Seeing all safety from the.

<unk> program.

A number a number of times and most of the Greenlight to proceed.

At the topline was simply to characterize accurately what we found in the six week double blind period, we'll actually have very specific data for you by the time, we come into world sleep in September.

In addition to that as Richard pointed out.

Logic exams with mobile we established baseline.

So that gives us some confidence there as well and then sort of Directionally as we said as we sort of said in our disclosure.

Great. Thanks for all the perspective.

Youre welcome.

Our next question is from the line of our cash to worry with Jefferies. Please proceed with your question.

Adverse event profile is in line with what we saw across the phase one healthy volunteer and patient cohorts from the Phase One program Hey, Paul Let me just add because it might anticipate some other questions. We're going to get just as a matter of fact, the safety database is actually not even closed until probably mid August because recall, we have a seven week extension that follows.

Richard Pops: We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or development.

Thanks, So much for the question. This is Anastasia onshore cash so in phase II looked like Takeda six one may have left some efficacy on the table and WT versus 99 core how confident are you that 2680 may be able to fully explore that exposure response range between four and eight makes 91 and differentiate on efficacy of our system.

Richard Pops: After our prepared remarks, we'll open the call for Q&A. And now let's turn the call over to Richard for some open...

Richard Pops: Thank you, Sandy.

The six week double blind, so actually we couldn't populate data tables with specific numbers until that database is locked so part of the reason for the level of disclosure at the at the at the at the topline was simply to characterize accurately what we found in six week double blind period, we'll actually have very specific data for you by the time, we come into world sleep in September.

Richard Pops: Good morning, everyone. We had a very successful second quarter. Our commercial and financial performance were strong. And last week, we took another major step forward in our pursuit of a medicine that has the potential to transform the treatment of narcolepsy. Now, midway through 2025, we're on track to deliver on our key objectives across the business. And commercial, we had planned for strong sequential growth and we exceeded our expectations in the second quarter. This result was driven by excellent operational execution by a seasoned commercial team. With sustained profitability now, no debt, and more than a billion dollars of cash, we're in a strong financial position with significant optionality.

<unk>.

Yes, we've always thought that a range of doses would be a competitive advantage and.

I'm not going to comment on the competitive programs I think that one of the features.

This program has always been the ability to dose across a wide range in NT, one leading into NTT NIH as well so we'll wait to see the data from the <unk> cohorts, but we're very pleased with the dose range that we selected for this <unk> one study.

Great. Thanks for all the perspective.

Youre welcome.

Our next question is from the line of our cash to worry with Jefferies. Please proceed with your question.

Thanks, So much for that question. This is Anastasia on for our cash so in phase two it looked like chocolate six one may have left some efficacy on the table and MW cheaper supply noncore. How confident are you that 26 80 may be able to fully explore that exposure response range between four and eight makes an empty one and differentiate on efficacy versus Takeda.

Thank you.

Our next question is from the line of Andrea <unk> with Goldman Sachs. Please proceed with your question. Good morning. Thanks for taking the question Rich I was just wondering if you might be willing to speak a little bit about how you are thinking about the regulatory path from here.

Richard Pops: It's clear to us now that the future growth of the business can be accelerated by the development candidates now in our pipeline. Last week, we reported positive top-line results from Vibrance 1. This was our first Phase 2 study of Elixirextin, which you've formerly known as ALK2680, in Narcolepsy Type 1. Vibrance 1 was successful and a critical study in the development of our Rexin portfolio, obviously for the efficacy and safety data it yields, but also for the operational foundation it provides for the Phase III program. Now, if you think back a year ago, we had data from our Phase 1B study of elixirexin that suggested robust efficacy and a generally well-tolerated profile based on single-day exposures across a range of doses in small cohorts of patients with narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia.

Thank you do you still need to meet with the FDA, but is there the possibility that these vibrant studies service Registrational trials.

Yeah.

Yeah, we've always thought that a range of doses would be a competitive advantage.

If not would you expect one registration enabling trial per indication would be sufficient to support approval or when do you need for each.

Well I'm not going to comment on the competitive programs I think that one of the features.

This program has always been the ability to dose across a wide range in N T. One leading into empty to NIH as well. So we'll wait to see the data from the <unk> cohorts, but we're very pleased with the dose range will be selected for this empty one study.

Good morning, Andrew and thank you for the question, Yes, I think okay.

First stipulation won't be that FDA has a fairly fluid place right now, but I'm going to answer the question based on what we know coming into into things and that is that our expectation was to complete the <unk> study.

And because we'll be seeking a label that encompasses narcolepsy writ large which would encompass and <unk>. We would wait for those data from NTT before scheduling our formal end of phase two meeting with FDA, where we.

Thank you.

Next question is from the line of Andrea <unk> with Goldman Sachs. Please proceed with your question. Good morning. Thanks for taking the question Rich I was just wondering if you might be willing to speak a little bit about how you're thinking about the regulatory path from here recognizing you do still need to meet with the FDA, but is there the possibility that these vibrant studies could serve as registrational trials.

Will agree on the phase III design. The reason we're doing that is because we're currently the only player in NTT at this late stage and so that's a very differentiating part of the of the product and potentially the label and as we understand the NT two doses relatively empty Windows is then we'll have the ability to sit down with the FDA and map out the phase III program.

Richard Pops: These data were critical in defining the initial clinical profile and dosing range for elixirextin. This was step one. Step two is to confirm and extend these observations in multi-week, multi-dose, phase two outpatient studies. Vibrance 1 in patients with narcolepsy type 1 is the first of these studies. Now, we have randomized, placebo-controlled, six weeks, multi-dose data in hand from more than 90 patients with NT1. We've now answered key questions in phase two with rigorous assays across larger cohorts of NT1 patients over a longer period of time. These data and insights will be fundamental in preparation for phase three.

If not would you expect one registration enabling trial per indication would be sufficient to support approval or would you need to for each.

Good morning, Andrew and thank you for the question, Yeah, I think okay.

Our assumption right now is that our phase III program will look very similar to the competitors I E. A three month study in N T. One and probably a similar study in an <unk> one each.

The first stipulation won't be that FDA has a fairly fluid place right now, but I'm going to ask the question based on what we know coming into it into things and that is that.

Our expectation was to complete the <unk> study.

And but we will confirm that in our end of phase II.

And because we'll be seeking a label that encompasses narcolepsy writ large which would encompass N. T went empty too we would wait for those data from NTT before scheduling our formal end of phase two meeting with FDA. We will agree on the phase III design. The reason we're doing that is because we're currently the only player in NT too at this late stage.

Yes.

Okay. Thank you.

The next question is from the line of Omar <unk> with Evercore ISI. Please proceed with your question.

Richard Pops: So here are the key findings from the study at the top line. First, the results demonstrated a significant effect on wakefulness and a generally well-tolerated profile. This was our pretest hypothesis, and the data were in line with our expectations. Second, the study provided entirely new and exciting findings relating to fatigue and cognition. These are among the most disruptive symptoms patients with narcolepsy experience, and they're distinct from excessive daytime sleeping. In this study, Elixirextin showed robust and clear improvements on validated patient-reported measures. Our view is that demonstrating effects in these domains establishes a new standard in the development of REXIN-2 receptor agonists in narco...

Guys. Thanks for taking my question.

Just two quick ones one could you confirm the dose response is in fact linear on M. W. T.

And so that's a very differentiating part of.

Of the product and potentially the label and as we understand the NTT doses relatively empty Windows is then we'll have a better ability to sit down with the FDA and map out the phase III program. Our assumption right now is that our phase III program will look very similar to the competitors I E. A three month study in N T, one and probably a similar stuff.

I ask because there's been some questions around the cataplexy observation and and my question is I realize there's a numerical trend, but it's not stat Sig at eight milligrams is it reasonable to assume based on how the data on the variability looked that you guys.

Trip the threshold on Pusan and ended up using negative binomial distribution to drive the P value ended that explained partially why P value was broader freight milligram. Thank you.

And in Q2, one one each.

And but we would confirm that in our end of phase two meeting.

Yes.

Good morning <unk>.

Yeah.

We haven't talked anything specifically about the linearity or lack thereof of the dose response, you'll actually see all of the all the by dose information in just a few weeks time at World sleep.

Okay. Thank you.

The next question is from the line of Omar <unk> with Evercore ISI. Please proceed with your question.

Richard Pops: These emerging data also further support our hypothesis that the erection system can be harnessed to address other neuropsychiatric and neurological conditions. We have two additional Erexin candidates that we plan to develop for conditions beyond central disorder disorders of hypersomnolence. In Q2, we initiated first in human studies for one of these candidates, ALKS4510. We plan to advance the second candidate, ALK7290, into the clinic later this year.

Hi, guys. Thanks for taking my question just two quick ones. One could you confirm the dose response is in fact linear on M. W. T and I ask because there's been some questions around the cataplexy observation and and and my question is I realize there's a numerical trend, but it's not stat Sig at eight milligrams is it reasonable to assume.

Statistical question on on Cataplexy is impossible for me to answer so I'll pass it to the pros.

Sure, Yes, I can answer that so we did use the negative binomial analysis and that was actually pre specified for us in conjunction with discussions with the FDA. So.

So we did use that analysis and pre specify it and based on our data that was the appropriate analysis to us.

Based on how the data on the variability looked that you guys.

Richard Pops: So for today, Craig and Marcus will take you through the top line results of VibranceOne, with significantly more detailed data to be presented at the upcoming World Sleep Meeting in September.

Trip the threshold on Pusan and ended up using negative binomial distribution to drive the P value ended that explained partially why P value was broader freight milligrams. Thank you.

So can I just clarify then Pusan was not your base case it won't it went straight into negative binomial.

That's correct that's correct yep.

Yeah.

Richard Pops: But first, Blair and Todd will review the financial and commercial performance of the business for the second quarter.

Wouldn't that create a discrepancy when we look at P values for Takeda data set versus alchemy dataset.

Numerous risks all all we haven't talked anything specifically about the linearity or lack thereof of the dose response, you'll actually see all the all the by dose information in just a few weeks time at World Sleep. Your statistical question on Cataplexy is impossible for me to answer so I'll pass it to the pros.

Blair Jackson: And with that, I'll hand the call over to Blair. Thank you, Rich. Our second quarter financial results were strong and reflected solid commercial and operational execution. We had planned for accelerated growth from the first quarter, and we exceeded our expectations. Financially, the year is progressing nicely, and we remain well-positioned to achieve our financial guidance for the full year, which we reiterated this morning. For the second quarter, we generated total revenues of $390.7 million. For our portfolio of proprietary products, we generated net sales of $307.2 million, reflecting 14% year-over-year growth. These results were driven by strong underlying demand, which Todd will address in his remarks, and gross-to-net favorability primarily related to Medicaid utilization rates and certain other credits during the quarter.

So it wouldn't be apples to apples on P value basis.

Yes, no it's a.

Good question I mean, we're not comparing apples to apples directly with their data set regardless, obviously they were different patient populations. So we wouldnt compare across trials directly.

Sure, Yes, I can answer that so we did use the negative binomial analysis and that was actually pre specified for us in conjunction with discussions with the FDA. So so.

But this is the analysis that we used in our pre specified and I would say that's one statistic that you use as a lens to look at the data when you go to world sleep Youll see other perspectives on that data that I think very clearly show Alexa reference effect on cataplexy at these doses. So for us if we think of as more of a mythological learning for phase III, which statistically.

So we did use that analysis and pre specify it and based on our data that was the appropriate analysis to us.

So can I just clarify then Pusan was not your base case it won't it went straight into negative binomial.

That's correct that's correct.

Which method or we can apply in phase III, recognizing we see a very clear cataplexy signal got it and Richard I'm sorry since.

Wouldn't that create a discrepancy when we look at P values for Takeda data set versus alchemy dataset.

So it wouldn't be apples to apples on P value basis.

Since this is so important I just want to be clear numerical trend wise you think the data is as competitive as Takeda.

Blair Jackson: These factors drove a one-time gross-to-net benefit of approximately $9 million for Vivitrol and approximately $11 million for Aristota. Taken together, these gross-to-net dynamics resulted in a proprietary product revenue tailwind of approximately $20 million in Q2. As we move into the third quarter, we expect Q3 net sales from this portfolio in the range of $280 to $300 million. Manufacturing and royalty revenues were $83.4 million for the second quarter, including revenues of $39.4 million from Boomerity and $30.3 million from the long-acting Invega product. Turning to expenses, cost of goods sold were $49.5 million, which compared favorably to $61.5 million for Q2 last year, primarily reflecting efficiencies following the sale of our Athlon-based manufacturing business last year.

Yes, no. It's a good question I mean, we're not comparing apples to apples directly with their dataset, regardless of obviously they were different patient populations. So we didnt compare across trials directly.

Cataplexy.

Again, it's apples and oranges. So what you can make the decision yourself when you see the data itself, but I think we feel quite comfortable that we have a clear cataplexy signal that youll see theres a theres. Some abrin, there's some outlier data that really confuses the.

But this is the analysis that we used in our pre specified and I would say that's one statistic that you use as a lens to look at the data when you go to the world sleep Youll see other perspectives on that data then I think very clearly show it looks erections effect on cataplexy at these doses. So for US if we think of as more of a mythological learning for phase III, which statistic in.

The statistic.

So you can try to correct for that using various statistical methods, where you can just look at the data and you'll see the data in more complete revelation.

At World Sleep, and I think we can talk about that afterwards, but I think you'd be satisfied that we have a very clear signal on cataplexy, just as an aside without without math associated with it remember the narcolepsy severity scale picks up cataplexy as one of its key domains and we've normalized patients on the NSS. So.

Which method or we can apply in phase III, recognizing we see a very clear cataplexy signal got it and Richard I'm, sorry, I'm. Since this is so important I just want to be clear numerical trend wise you think the data is as competitive as Takeda.

All the data it tended to work complementary.

Cataplexy.

Again, it's apples and oranges. So what you can make the decision yourself when you see the data itself, but I think we feel quite comfortable that we have a clear cataplexy signaled that youll see theres a theres some aberdeen, there's some outlier data that really confuses the statistic.

Blair Jackson: R&D expenses were $77.4 million compared to $59.6 million for Q2 last year, reflecting investments in the Vibrance Phase II studies of elixirexin across narcolepsy and idiopathic hypersomnia. We expect R&D expense to step up slightly in the second half of the year as we complete our Phase 2 studies in narcolepsy and continue to build momentum in our Phase 2 study in idiopathic hypersomnia. SG&A expenses were $170.8 million compared to $168.1 million for Q2 last year. For trending purposes, we expect SG&A expense to be fairly consistent in Q3 and a modest decrease in the fourth quarter of the year.

Thank you Youre.

Youre welcome.

Our next question comes from the line of Jessica Fye with Jpmorgan. Please proceed with your.

Your question.

Hello. This is Adam on for Josh. Thank you for taking our question.

So you can try to correct for that uses mirrors to cynical message, where you can just look at the data and you'll see the data in more complete revelation at.

Just wanted to ask.

Yes.

Alright.

Excuse me a lesser extent could.

At World Sleep, and I think we can talk about that afterwards, but I think you'd be satisfied that we have a very clear signal on cataplexy, just as a as an aside without without math associated with it that remember the narcolepsy severity scale picks up cataplexy as one of its key domains and we've normalized patients on the NSS. So.

Could you please remind us of the potency selectivity towards the Oh X two are over the <unk>. One are thank you.

Kind of my thought she has had a pronounced <unk> because it's not the easiest where different now.

5000 fold.

So it's 5000 fold more selective.

All the data it tends to.

Yeah.

Work complementary.

Great. Thank you.

Blair Jackson: This performance generated strong profitability of GAAP net income of $87.1 million, EBITDA of $101.6 million, and adjusted EBITDA of $126.5 million in the second quarter. Turning to our balance sheet, we ended the quarter in a strong financial position with $1.05 billion in cash and total investment. We continue to have $200 million of remaining share repurchase authorization and going forward we may opportunistically repurchase shares dependent on market conditions and the capital needs of the business. As we look ahead, based on our performance during the first half of the year and the expected contribution from our expanded sales efforts, we're on track to deliver record revenues from our portfolio of proprietary products in 2025.

Thank you.

Our next question is from the line of Joseph Thome with Cowen. Please proceed with your question.

Youre welcome.

Our next question comes from the line of Jessica Fye with JP Morgan.

Hi, there.

Good question.

Congrats on the progress and thank you for taking my question, maybe when we do look at the full safety profile of <unk> and maybe how much of that can be extrapolated to some of your follow on compounds 45, 10, and 70 to 90. It looks like there's obviously some class orexin side effects that we're seeing but is there anything different about the targeting or the dosing of $45 10.

Hello. This is Adam on for Josh. Thank you for taking our question.

Just wanted to ask.

Uh huh.

Excuse me I'm extra accidents could you please remind us of the potency selectivity towards the Oh X two are over the <unk>. One are thank you.

$70 90 that you think could result in a difference AE profile or I guess, how much will <unk> initial data derisked follow on obviously, we need to see the data, but how do you think about trend liability there.

And am I thought she has had a pronounced that likes orexigen, because it's not the easiest where different now.

Bob.

So it's 5000 fold more selective.

Go ahead Margaret.

Great. Thank you.

We think.

Yes, they are there.

Our next question is from the line of Joseph Thome with Cowen.

Blair Jackson: As a result of this strong performance, we now anticipate finishing the year towards the higher end of our previously issued financial expectations in terms of both revenue and profitability.

They are working on the same receptor. So we do think there will be some similarities that being said the molecules were purposely developed to have different pharmacokinetic profiles and different <unk>.

Your question.

Hi, there.

Good morning, Congrats on the progress and thank you for taking my question, maybe when we do look at the full safety profile of <unk> and maybe how much of that can be extrapolated to some of your follow on compounds 45, 10, and 70 to 90. It looks like there's obviously some class a orexin side effects that we're seeing but is there anything different about the targeting or the dosing of 45.

Todd Nichols: With that, I'll turn the call to Todd for review of the proprietary portfolio. Thank you, Blair. And good morning, everyone. In the second quarter, we recorded net sales from our proprietary product portfolio of $307.2 million. reflecting 14% year-over-year growth. We drove strong in-market demand across Vivitrol, Aristata, and Libalvi by executing targeted growth initiatives. and deliver strong sequential growth from Q1 to Q2. Due to this demand growth and the growth to net favorability during the quarter that Blair outlined. Our second quarter proprietary net sales.

Different structures that.

Could lead them to not all look exactly the same on a on the AE.

A profile so of course, the human data will answer that question for us completely and we hope to have that for you in the near future on both 45 10 and 72.

$7 90 that you think could.

And Joe if you don't mind, let me build on your question because you anticipate questions. We've been getting from investors and that is how do the <unk> one data anticipate what we'd seen NTT.

And the difference AE profile or I guess, how much will the elixir exit initial data derisked follow on obviously, we need to see the data, but how do you think about trying to liability there.

And I think I, just want to make clear our original hypothesis, which has been confirmed by our own data, which is we believe that theres actually a frame shift in terms of the tolerability and sensitivity to Orexin agonist as you move from <unk> to NTT, meaning youll need higher doses to drive efficacy and youll need higher doses to drive the on target side effects.

Go ahead Mark.

We think.

Yes, they are there.

They're they're working on the same receptors. So we do think there will be some similarities that being said the molecules were purposely developed to have a different pharmacokinetic profiles and different different structures that.

Todd Nichols: The $307.2 million exceeded the expectations that we provided in May of net sales in the range of $260 to $280 million.

As well so we imagine just the dose response curve shifting to the right in that and Thats. What it is consistent with the data we saw in our phase <unk> study, we will know more definitively obviously, when we get those data, but that's the pretest hypothesis.

Could lead them to not all look exactly the same on all of them.

Todd Nichols: Starting with Vivitrol, net sales in the second quarter were $121.7 million. Vivitrol performance continues to be driven by growth in the alcohol dependence indication market and our ability to capitalize on highly localized market dynamics. certain states and pair. Looking ahead, we continue to expect Vivitrol net sales for the full year 2025 in the range of $440 to $460 million.

AE profile. So of course, the human data will answer that question for us completely and we hope to have that for you in the near future on both 45 10 M 72.

Perfect. Thank you.

The next question is from the line of <unk> with Mizuho Securities. Please proceed with your question.

And Joe if you don't mind, let me build on your question because you anticipate questions. We've been getting from investors and that is how do the <unk> one data anticipate what we've seen in <unk> and I think I just want to make clear our original hypothesis, which has been confirmed by our own data, which is we believe that there's actually a frame shift in terms of the tolerability and sensitivity to <unk>.

Hey, guys, yeah, thanks for taking our question.

Given that the MTT study I guess the primary endpoint.

Complete expects to conclude.

August just wondering is there a good chance that youre still present, the NTT data at world sleep. Thanks.

Todd Nichols: Turning to our psychiatry franchise. The expansion of our psychiatry sales force completed earlier this year was an important element of our strategy to maintain a competitive share of voice for Lee Balby and re-accelerate growth for Aristotle. The early returns from that expansion are encouraging and we are pleased with our progress today. For the Aristotle product family, in the second quarter, net sales were $101.3 million. Leading indicators related to underlying demand were encouraging with increased prescriber breadth and strong new-to-brand prescriptions during the quarter. For the full year 2025, we continue to expect Aristotle net sales in the range of $335 to $355 million.

Orexin agonist as you move from <unk> to empty too, meaning you'll need higher doses to drive efficacy and you'll need higher doses to drive the on target side effects as well. So we imagine just the dose response curve shifting to the right in that and that's what it is consistent with the data we saw in our phase <unk> study, we will know more definitively obviously, when we get those data but that's.

Just to be clear so we should complete enrollment in the next couple of weeks, which then with a two week with a two month primary analysis puts us into the fall. So there won't be any NTT data at world sleep there'll be plenty of empty one to review so.

You won't you won't be hungry.

The pretest hypothesis.

Yes.

Thanks.

Perfect. Thank you.

The next questions are from the line of David <unk> with Piper Sandler. Please proceed with your question.

The next question is from the line of eye ear with Mizuho Securities. Please proceed with your question.

Hey, Thanks, So number one are you planning to build in dosing flexibility or any sort of titration.

Hey, guys, yeah, thanks for taking our question.

Given that the MTT study I guess the primary endpoint.

In the phase three as a means of minimizing treatment emergent adverse events.

It's completely expects to conclude.

Todd Nichols: Turning to libality, net sales grew 18% year-over-year to $84.3 million. Underlying TRX growth was 22% year-over-year, driven by new patient starts and prescriber breadth. Gross to net adjustments were approximately 29% in the second quarter. We now expect gross to net adjustments for the full year will be approximately 30%. For the full year, we continue to expect evolving net sales in the range of $320 to $340 million. Across the portfolio, we are pleased with our second quarter performance and are focused on maintaining this momentum and driving demand in the second half of the year.

August just wondering.

And then secondly, this is a commercial question.

Theyre a good chance that you also presented <unk> data at World sleep.

It's not of course unheard of to have a wakefulness promoting agent that does not have cataplexy in the label I guess my question here is just given the wakefulness promoting properties of <unk>. How important is it to have cataplexy in the label in terms of commercial adoption perspective.

Well, we'd just be clearer. So we should complete enrollment in the next couple of weeks, which should then with a two week with a two month primary analysis puts us into the fall. So there won't be any NTT data at world sleep there'll be plenty of N T. One to review so.

You won't you won't be hungry.

Yeah.

Thanks.

Thank you.

The next questions are from the line of David <unk> with Piper Sandler. Please proceed with your question.

So <unk> morning, David.

I'll give you my view and then I'll hand, it over to the guys. We haven't made that call yet on the phase III dosing because we haven't finished all of the analyses and we also want to see the NTT dosing data before we decide on a range of doses.

Hey, Thanks, So number one are you planning to build in dosing flexibility or any sort of titration.

Craig Hopkinson: With that, I will pass the call to Craig. Thank you, Todd. Last week, we announced positive top-line results from the Vibrance One Phase 2 study of elixir rextin in patients with narcolepsy type 1. The data further characterized the clinical profile of elixirextin and demonstrated that once-daily elixirextin normalized wakefulness and excessive daytime sleepiness scores in highly symptomatic patients with narcolepsy type 1 with a generally well-tolerated profile across all doses tested. These top-line results represent the first of a series of datasets that will emerge from the Alexa Rexton Phase II program. The data are extensive and break new ground.

In the phase three as a means of minimizing treatment emergent adverse events.

So stay tuned there we have.

What's so exciting about running phase twos of this quality is and now we have 92 patients worth of data to model.

And then secondly, this is a commercial question.

And our view is that that level of exposure time.

It's not of course unheard of to have a wakefulness promoting agent that does not have cataplexy in the label I guess my question here is just given the wakefulness promoting properties of <unk>. How important is it to have cataplexy in the label in terms of our commercial adoption perspective.

Is essential for actually making those dosimetry decisions for the Registrational program. So stay.

Stay tuned on that wakefulness that my own view and Todd can answer the question is that we will.

It looks orexin is going to have a cataplexy claim in the label because the signal is quite clear. So it's more a matter of of tuning the assay to make sure that we can we can see that in the data, but Todd you can comment on whether you think cataplexy is an important part of the presentation I agree I think you captured it right okay.

Thank you.

So <unk> morning, David.

I'll give you my view and then I'll hand, it over to the guys. We havent made a call yet on the phase III dosing because we haven't finished all the analyses and you also want to see the NTT dosing data before we decide on a range of doses.

Craig Hopkinson: We are looking forward to presenting the primary and key secondary endpoints related to wakefulness and cataplexy and the safety and tolerability profile observed in the six-week double-blind period of the study in an oral presentation at the upcoming World Sleep Meeting at the beginning of September. In addition to the top-line results, we'll also share data relating to the exploratory patient-reported outcomes collected in Vibrance One, including the fatigue and cognition data outlined in our top-line press release last week. These data are truly exciting, not only in terms of the clinical profile for Oryxorexin, but also as we plan for additional clinical studies across our portfolio of investigational Oryxin-2 receptor agonists in disorders where impaired cognitive functioning and fatigue are key clinical features.

Alright. Thanks.

So stay tuned there we have.

The next question is from the line of David Ho with Deutsche Bank. Please proceed with your question.

What's so exciting about running phase twos of this quality is and now we have 92 patients worth of data to model.

Hi, congrats on the quarter and taking my question.

So I just wanted to ask about the upper dose in the NTT <unk> studies I believe at 18 milligrams could you just remind us.

And our view is that that level of exposure time.

It is essential for actually making those dosimetry decisions for the Registrational program. So.

How you landed on <unk>, specifically given 25, we used in the earlier phase one be and what would be I guess, the ideal number to take forward into phase III.

Stay tuned on that wakefulness.

My own view and Todd can answer the question is that we will Oh looks orexin, that's going to have a cataplexy claim in the label because the signal is quite clear. So it's more a matter of of tuning the assay to make sure that we can we can see that in the data, but Todd you can comment on whether you think you can.

Greg you want to talk about.

We employed some sophisticated modeling basically taking into account all the data that we had collected from our healthy volunteer studies as well as.

Cataplexy is an important part of the presentation I agree I think you captured it right okay.

Our phase one b.

Our program and ultimately modeled out the doses for phase two.

Alright. Thanks.

The next question is from the line of David Ho with Deutsche Bank.

Craig Hopkinson: Following World Sleep, we expect top-line results from Vibrance 2, our Phase 2 study in narcolepsy type 2 in the fall. Enrolment in Vibrance 2 is going well and we expect to complete that soon. Top-line data from Vibrance 3, our Phase 2 study in idiopathic hypersomnia, are expected to follow in mid-2026. Each of these studies provides a significant amount of data to analyze and will deepen our understanding of elixirexin's potential utility across central disorders of hypersomnolence and its differentiating features in the competitive landscape. In parallel, we are preparing for key regulatory interactions and for the Global Phase III program in narcolepsy that we plan to initiate as rapidly as possible following the top-line data from the Narcolepsy Type 2 study.

And Thats, how we come to the dose selection.

To your question.

Thank you the.

Hi, congrats on the quarter and taking my question.

The next question is from the line of Javier <unk> with Needham <unk> company.

So I just wanted to ask about the the upper dose in the NTT <unk> studies I believe at 18 milligrams could you just remind us how.

With your question.

Good morning, Thanks for taking my question.

Going back to the <unk>.

How you landed on <unk>, specifically, given 25 was used in the earlier phase one b and and what would be I guess, the ideal number to take forward into phase III.

Focus on vision East can you give us sort of high level view on how important is it to.

Avoid dulles, Scott might have such and even if it were to be transient.

Greg you want to talk about it so.

We employed some sophisticated modeling basically taking into account all the data that we had collected from our healthy volunteer studies as well as.

And would you choose to take a dose interfaith CE that might've seen <unk> integration office event.

Our phase one b.

Separately speaking.

We think that that is an on target effect of this class.

Graham and ultimately modeled out the doses for phase two.

And.

And that's how we come to the dose selection.

And as you think about sort of your next Gen assets do you think that could suggest a broadly on target exactly mark.

Craig Hopkinson: Alkermes is at the forefront of development in this exciting potential therapeutic category and the positive Vibrance I data represent an important stride forward for Elexorexin development program and our broader portfolio of Orexin-2 receptor agonists.

Thank you.

This mix too.

The next question is from the line of Ami <unk>.

The structure also different drug thank you.

Yet with Needham and company.

Let me start off I'm, just going to try to pull you back up from the visual AE obsession to the question on <unk> in General I mean, what we're looking at in this data set is doses, where we know there are on target to ease, namely insomnia and poly carrier.

With your question.

Good morning, Thanks for taking my question.

Marcus Yance: With that, I'd like to introduce Dr. Marcus Janss to review the top-line data from the Vibrance One study. Marcus is Vice President of Clinical Development and the Clinical Program Lead for Elixir-Extant Carot Alkermes. Marcus. Thank you, Craig. Vibrance 1 is a six-week, double-blind, placebo-controlled, parallel design study evaluating three different doses of elixirextin in patients with narcolepsy type 1, or NT1. The study enrolled a total of 92 patients, with most having moderate to severe disease at base level. Patients were randomized to one of three once-daily dose levels of elixirextin, four, six, or eight milligrams, or placebo.

Going back to the focus on vision East can you give us sort of a high level view on how important is it to.

And others have observed is on target effects that could be there.

<unk> a dose that's my task question, even if it were to be transient.

We live with limit your dose so I think the virtue of this program that we've run three different doses for six week periods of time in the outpatient setting and will get a complete time course as well as severity map of those of those aes.

And would you choose to take a dose interface CE that might've seen at Changi installation office event.

And just separately speaking do you think that that is an on target effect of this class.

We have so much more data to look at it together because let's say for example, if you are a numerical AE.

And you know.

And as you think about sort of your next Gen assets do you think that could suggest a broadly on on target exactly that's more specific to.

Did it happen every day over the over the 42 doses or did happened once in the first week and then went away.

Theres a lot of nuance to this so I don't think it's easy to answer the question about what doses, we would take forward because I think that there is a range of different aes that were going to be focusing on there and we think our competitive advantage is going to be this range of doses because not all patients are the same and people react to different doses and I think that that would be true for efficacy as well as for for Aes.

The structure also different drug thank you.

Marcus Yance: The primary endpoint of Vibrance 1 was the change from baseline compared to placebo in the maintenance of wakefulness test or MWT. MWT is a standardized, quantitative measure of how long patients can stay awake during a 40-minute test period when they're in an environment that is conducive to sleep. These tests are conducted at 2, 4, 6, and 8 hours post-dose. The mean score is calculated by averaging the results of these four tests. While the MWT is less frequently used in real-world clinical settings, it is an important objective endpoint commonly used for regulatory purposes. In Vibrance 1, elixirextin showed dose-dependent, statistically significant, and clinically meaningful increases in mean sleep latency at all doses tested at week 6.

Let me start off I'm, just going to try to pull you back up from the visual AE obsession to the question on <unk> in General I mean, what we're looking at in this data set is doses, where we know there are on target to ease, namely insomnia and Poly Korea that we and others have observed is on target effects that could be there.

Marcus you don't have your view on it yes.

Yes, yes, I would agree.

Liquid limit your dose so I think the virtue of this programs that we've run three different doses for six week periods of time, the outpatient setting and we will get a complete time course as well as severity map of those of those aes and it we have so much more data to look at it together because let's say for example, if you are a numerical.

As we speak doing complicated modeling on exposure response exposure safety analyses and thats going to encompass everything we've seen where we're looking at this data in every way we can to to help us determine what the best range of doses is going to be to move forward into phase III. So that's going to encompass.

He did.

Does it happen every day over the over the 42 doses or did happened once in the first week and then went away.

Because it is going to encompass safety.

And.

Even ease of ease of dosing and so we're thinking about at all.

There's a lot of nuance to this so I don't think it's easy to answer the question about what doses, we would take forward because I think that there's a range of different aes or we're gonna be focusing on there and we think our competitive advantage is going to be this range of doses because not all patients are the same and P people react to different doses and I think that that would be true for efficacy as well as for for Aes.

Possible criteria, when we think about dosing moving forward.

Marcus Yance: Importantly, all of those groups achieved normative wakefulness, applying the standard convention of a mean sleep latency on the MWT of 20 minutes or more. The study also evaluated key secondary and including change from baseline on the Epworth sleepiness scale and weekly cataplexy rates compared to placebo. First, the Epworth Sleepiness Scale, or ESS. Unlike the MWT, this scale is widely used in the clinic as a diagnostic tool to assess for excessive daytime sleep. The ESS is a patient-reported symptom questionnaire asking about the patient's likelihood of falling asleep across eight different scenarios, such as watching TV, riding in a car, or reading a book, over the last week.

Thank you.

The next question is from the line of Ash pharma with UBS. Please proceed with your question.

Oh, Hi, Thanks funding my question. So just on these phase two studies.

Marcus you I'm happy to hear your view on that.

Yes, yes, I would agree were.

Ah patients dosed with <unk> I understand your stone in the outpatient setting.

As we speak doing complicated modeling on exposure response exposure safety analyses and thats going to encompass everything we've seen where we're looking at this data in every way we can to to help us determine what the best range of doses is going to be to move forward into phase III. So that's going to encompass.

For the <unk>, but.

But just what's your dedication to the patients.

And then secondly, under visual disturbance that you mentioned, so the PRC and that you're not seeing any signal, but as that state and based on <unk> that you may have seen in.

Efficacy, it's going to encompass safety.

And outside of the schedule exams.

And.

Thanks.

Even ease of ease of dosing and so we're thinking about at all.

Marcus Yance: Higher scores indicate a greater likelihood of falling asleep, with a score of 10 and below considered normal. The Epworth scale is useful in that the 7-day look-back period provides a holistic view of patient sleepiness beyond the 8-hour MWT test period. Here, across all doses tested, elixirextin demonstrated statistically significant and clinically meaningful improvement at week 6, with each dose group achieving normative levels. In addition to excessive daytime sleepiness, NT1 patients can experience a sudden involuntary loss of muscle tone called cataplexy. Vibrance 1 evaluated mean weekly cataplexy rate. To measure this end point, patients are asked to keep diaries of cataplexy events that they experience.

Sure I can answer the first part so we tell them generally to take it in the morning, so roughly around eight a M. There's of course, a window around that just to.

Possible criteria, when we think about dosing moving forward.

Thank you.

To accommodate for various lifestyles, but roughly eight am in the morning is when we ask them to dose.

The next question is from the line of Ash pharma with UBS. Please proceed with your question.

And we didn't do me any specific AE table.

Oh, Hi, Thanks funding my question. So just on these phase two studies.

Elements until the face.

One I am sorry until the phase II safety database is close in mid August So youll see those data at world sleep in September.

The day Ah patients dosed with <unk>.

Finished down in the outpatient setting.

Yeah.

On the <unk>.

Thank you.

But just what's your dedication to the patients.

The next question is from the line of Leonid Tamasha with RBC capital markets. Please proceed with your question.

And then secondly on the visual disturbance that you mentioned, so the PRC that you're not seeing any signal, but as that state and based on <unk> that you may have seen in and outside of the schedule exams.

Alright, Thanks, guys I just wanted to ask on the endpoints just given what you've seen out of Vibrance. One are you still thinking that.

The best way to go forward.

Marcus Yance: The average number of weekly events across weeks 5 and 6 in the ELIXIR-X-TREATED subjects were then compared to those experienced by the placebo group. Across all doses tested, elixirextin showed numerical and clinically meaningful improvements in cataplexy compared with placebo, and on the pre-specified analysis, met the threshold for statistical significance at the 6 mg dose. We are confident in the effects of elixir-X in on cataplexy and believe there are learnings here related to our implementation of this assay that we will apply in phase three to reduce variability and the impact of outliers.

Thanks.

Financing sure I can answer the first part so we tell them generally to take it in the morning, so roughly around eight a M. There is of course, a window around that just to.

Compared to SaaS.

Both for any as you think about I guess the.

Dual designed for Vibrance to and then the USS focus for Vibrance, three and then related to that given all of the secondaries that you hit on including some of the exploratory is how are you thinking about elevating some of those exploratory endpoint secondaries are key secondaries for a phase III program like cognition or fatigue and would you try to aim to get those on.

To accommodate for various lifestyles, but roughly eight am in the morning is when we ask them to dose.

And we didn't do me any specific AE table.

Elements until the face.

One I am sorry until the phase II safety database is close in mid August so you'll see those data at world sleep in September.

The label Thanks.

Yes.

Yeah.

So.

From our perspective, we believe both <unk> and <unk> are really important measures aimed.

Yeah.

Thank you.

Question is from the line of Leonid Tamasha with RBC capital markets. Please proceed with your question.

Marcus Yance: We look forward to sharing additional analyses of these data at world. So while excessive daytime sleepiness is the hallmark symptom of narcolepsy, many patients also experience other symptoms such as fatigue and cognitive dysfunction. These can result in significant morbidity as well as impaired quality of life. Our hypothesis has been, given the nature of the neurocircuitry affected, that elixirextin could have an impact on many of the aspects of this disease that affect patients' day-to-day function. The British Columbia Cognitive Complaints Inventory, or BCCCI, and the Promise Fatigue Scales capture two of these common and often debilitating effects of narcolepsy.

<unk>, obviously, the more objective measure it with a <unk>.

Thanks, guys I just wanted to ask on the endpoints just given what you've seen out of Vibrance. One are you still thinking that M. W. T is the best way to go forward.

Really sort of expressing the patients to the subject of assessments. The reason that we elevated epworth to.

Compared to assess both for any as you think about I guess the.

Primary in the NTT study.

Is because of our sort of thought process around.

Dual designed for Vibrance to and then the USS focus for Vibrance, three and then related to that given all the secondaries that you hit on including some of the exploratory is how are you thinking about elevating some of those exploratory endpoint secondaries.

Planning for regulatory interactions really taking a look at the late stage clinical trial landscape and planning for our phase three program. So yes, we believe both of our importance and I think the data from the <unk> study.

Secondaries are key secondaries for a phase III program like cognition or fatigue and would you try to aim to get those on the label.

<unk> will help us plan for a phase III program with the with the dual primary endpoints.

Great.

So.

From our perspective, we believe both <unk> and WT and airports are really important measures.

And on the key secondaries markets, you might want to comment on but from my perspective. These were really exploratory and some of the skills that I don't think have been used in narcolepsy studies at all and so we were curious to see whether we would see movement.

Marcus Yance: The BCCCI evaluates concentration, memory, expressing thoughts, word finding, slow thinking, and difficulty solving problems. The promised fatigue measures patient's frequency, as well as intensity of fatigue, along with its impact on physical, mental, and social activity. It's important to note here that fatigue is a symptom that patients experience, which is distinct from sleepiness. While sleepiness is a general feeling of being tired and wanting to sleep, fatigue is a broader feeling of exhaustion that can be long lasting and may not be resolved by sleep. We also looked at the narcolepsy severity scale. The NSS captures a holistic assessment of disease.

M WT obviously.

More objective measure it with.

Really sort of expressing the patients to the subject of assessments. The reason that we elevated effort to.

And boy did we I mean, we really saw clear signals and Youll see more of those data at world sleep.

Given the magnitude of the response and how clear it was I think we have to do a lot of thinking now about how we might elevate those in the hierarchy. Please comment on it exactly right rich and where the teams here working.

Primarily in the <unk> study.

Because of our sort of thought process around.

Planning for regulatory interactions really taking a look at the late stage clinical trial landscape and planning for our phase three program. So yes, we believe both of our importance and I think the data from the <unk> study.

Gently to look at exactly that all of these various exploratory outcomes the ones, where we <unk>.

Succeeded that again.

Hypotheses that we've we've now shown significant data on and so the team is really working on how do we pull these end through the phase III and elevate them into the key secondary realm.

<unk> will help us plan for a phase III program with the with the dual primary endpoints.

Marcus Yance: by evaluating five key narcolepsy. Excessive Daytime Sleepiness, Cataplexy, Hallucinations, Sleep Paralysis, and Disturbed Nighttime Sleep. And on each of these exploratory patient reported outcome scales, the BCCCI, the PROMIS-FATIGUE, and the NSS, elixirexin demonstrated clinically meaningful improvements from baseline compared to placebo that were statistically significant. Of course, the p-values here are nominal due to the exploratory nature of these individuals. So from a clinical perspective, these results are compelling due to the robustness and particularly the consistency across all doses of elixirexin, as well as across various complementary assays. This is the first time that we've seen data from the orexin class on these fatigue and cognition scales.

And on the key secondaries markets, you might want to comment on but from my perspective. These were really exploratory and some of these skills at I don't think had been used in narcolepsy studies at all and so we were curious to see whether we would see movement.

In a way that.

That allows us to really test the aspects of this drug more thoroughly.

And boy did we I mean, we really saw a clearer signals and youll see more of those data at world sleep.

Thank you.

The next question comes from the line of Jason <unk> with Bank of America.

Yeah.

Given the magnitude of the response and how clear it was I think we have to do a lot of thinking now about how we might elevate those in the hierarchy. Please comment on it exactly right rich and where the teams are here working.

Hey, guys. Good morning, guys for taking my question so.

Just wanted to probe a little bit just your understanding of the.

Our relationship with PK and the weekly cataplexy endpoint.

And whether or not you feel comfortable enough to rollout.

Gently to look at exactly that all of these various exploratory outcomes the ones, where we <unk>.

QD versus bid approaches conferring any advantage in terms of the WCS measurement and then also just I know youre not commenting on phase III dosing plans, yet wanting to see the <unk> results first but I'm wondering if we can take from your comments.

<unk> exceeded that again were.

I policies that we've we've now shown significant data on and so the team is really working on how do we pull these end through the phase III and elevate them into the key secondary realm.

Marcus Yance: And we believe this differentiates elixirexin from other development programs and builds upon the evidence base that orexin 2 receptor agonists with appropriate pharmaceutical properties could have broad potential utility across a range of neurological or neuropsychiatric disorders.

In a way that.

That at least in the context of empty one that there is at least enough confidence in the tox profile of the high eight Meg dose.

That allows us to really test the aspects of this drug more thoroughly.

You could potentially push dose and future <unk> pivotal thanks.

Thank you.

Marcus Yance: And now we'll turn to safety and tolerability. Overall, elixirextin was generally well-tolerated in this study. The majority of the treatment-emergent adverse events were mild to moderate in severity, and no treatment-emergent serious adverse events were seen. The TEAEs that did occur were generally consistent with the events that we observed across the Phase I studies in healthy volunteers and in subjects with NT1, NT2, and IAEA. And among the many clinical safety assessments we conducted in the study, two of particular interest are hepatic labs and ophthalmic exams. And importantly, there were no treatment emergent safety signals seen in these assessments.

The next question comes from the line of Jason <unk> with Bank of America.

Hey, guys wanted to talk about the PK WC, our religion sure I mean at this point those analyses are ongoing so we've reported as you know sort of the the top line results and were really.

Yeah.

Hey, guys. Good morning, guys for taking my question so.

Just wanted to probe a little bit just your understanding.

The relationship with PK and the weekly cataplexy endpoint.

Digging deeper into the PK again, as I mentioned sort of exposure.

And whether or not you feel comfortable enough to rule out.

Exposure response exposure safety, so so thats.

QD versus bid approaches conferring any advantage in terms of the WCS <unk> measurement and then also just I know youre not commenting on phase III dosing plans, yet wanting to see the <unk> results first but I'm wondering if we can take from your comments that.

Going to be coming soon and puts into something you'll see in the future, but is it fair to say Mark I don't think Theres, a QD versus the <unk>.

So we think is meaningful we don't know that's right yes.

And.

With respect to the phase III dosing financing.

At least in the context of MQ, one that theres at least enough confidence in the Tox profile of the high eight Meg dose.

Yes.

Marcus Yance: So overall, we are very pleased with the safety and efficacy profile thus far.

At this point for phase III dosing again, we're still we're still making those determinations. So it's hard to speak to them. We do have confidence fully in our tox profile of eight milligrams. So there's there's no concern there and where we are obviously taking that into account as well as everything else, we've talked about to determine our phase III doses.

Marcus Yance: And we look forward to presenting these data sets at World's.

You could potentially push dose and future <unk> pivotal thanks.

Richard Pops: I'll hand it back to you, Rich. Well done. Thank you, Marcus. So that's a summary of the top-line findings.

Hey, you guys. When it came out talking about PK WC, our religion sure I mean at this point those analyses are ongoing so we've reported as you know sort of the the topline results and where we're really.

Richard Pops: There's a lot more to come, and you'll begin to see it in a few weeks at WorldSleeve. These data in NT1 represent a meaningful step forward for the ELLICSO-Rextin development program, and they provide a substantial new data set that significantly expands our understanding of orexin biology, not just relevant to narcolepsy, but it's potential across a broad range of neuropsychiatric and neurological disorders. We're now moving forward with confidence and a sense of urgency as we prepare for the initiation of our registrational program in Narcolepsy. And with clear findings now relating to cognition and fatigue, adding to what we've seen for excessive daytime sleepiness, we now have further data supporting development of additional orexin candidates in other disease states beyond sleep disorders.

Got it thank you.

The next question is from the line of requirement with Baird. Please proceed with your question.

Digging deeper into the PK.

So could you be have you.

Again, as I mentioned sort of exposure.

Yeah.

Oh, I'm, sorry, I was on mute.

Exposure response exposure safety, so so thats.

Alright, just a quick one for me it looks like some nice step ups in revenues across the board can you just talk about the relative contribution from into inventory or seasonal dynamics as compared to underlying demand for the commercial portfolio. Thank you.

Going to be coming soon and potentially something youll see in the future, but is it fair to say Mark I don't think Theres, a QD versus the.

Difference, who we think is meaningful we don't know that's right yes.

This is Blair I'll start with on the number of basis and I'll turn it over to Todd to get into some detail I think number one as you look at our proprietary programs. We saw demand increase across all all three programs over over the time period, we actually didn't have any inventory dynamics that contributed to this quarter.

And.

With respect to the phase II dose financing.

I mean at this point for phase III dosing again, we're still we're still making those determinations. So it's hard to speak to them. We do have confidence fully in our tox profile of eight milligrams. So there's there's no concern there and where we are obviously taking that into account as well as everything else, we've talked about to determine our phase III doses.

Richard Pops: As you've heard throughout this call, the business is in a strong position. Our commercial team is on track to deliver proprietary product next sales in excess of a billion dollars and robust profitability in 2025. Our balance sheet is strong and provides strategic optionality with more than a billion dollars in cash. Our pipeline products are advancing. Elixirextin is the first major potential commercial opportunity to emerge from our Erextin portfolio. But we also believe that sleep disorders are just the beginning for this exciting new therapeutic category.

And so this is in line with normal seasonal dynamics and contribution of our strong commercial performance, but anything you want to yeah. I would just agree with what Larry said, we saw strong demand for all three products are sort of <unk> and we were really pleased with Q2 was really a step up in new patients.

Got it thank you.

The next question is from the line of requirement with Baird. Please proceed with your.

Question.

Luke do we have you.

<unk> as we said earlier exceeded our expectations to Blair's point nothing to look at with inventory inventory is growing with demand right. Now so we're pleased with that.

Yeah.

Richard Pops: So thank you for your patience.

Oh I'm, sorry, I was on mute sorry, just a quick one for me it looks like some nice step ups in revenues across the board can you just talk about the relative contribution from inventory or seasonal dynamics as compared to underlying demand for the commercial portfolio. Thank you.

Sandra Coombs: With that, I'll turn the call back to Sandy to run the Q&A. Great. Thanks, Rich.

Unknown Executive: Rob, we'll now open the call for Q&A, please. Thank you, Sandy. We'll now be conducting a question and answer session.

Great. Thank you.

Thank you.

Unknown Executive: To allow as many analysts to ask questions as possible, we ask that you please limit yourself to one question. If you'd like to ask a question at this time, you may press star 1 on your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to withdraw your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Thank you.

Our last question comes from line of Marc Goodman with Leerink Partners. Please proceed with your question.

Yeah. This is this is Blair I'll start with on the number basis and I'll turn it over to Todd to get into some detail I think number one as you look at our proprietary programs. We saw demand increase across all all three programs over over the time period, we actually didn't have any inventory dynamics that contributed to this quarter.

Yes, just back on this cataplexy endpoint discussion what when you talked about the learnings for the phase III are these learnings basically just the statistical methods that you were talking about are you talking about equal different assays.

Confused maybe for Sean.

A little more light there I mean, we're all still a little confused what happened with the cataplexy data and we're wondering like are we even got to learn.

And so this is in line with normal seasonal dynamics and contribution of our strong commercial performance.

Paul Matteis: And our first question today comes from the line of Paul Matteis with Stiefel. Please proceed with your question. Hey, good morning. Thanks so much for taking my question and congratulations on all the progress.

Once we once we see the data in Singapore, we're going to feel much better about it I mean, because you were talking about statistical significance and what needs to get on the label like doesn't it needs to be stat Sig to get on the label I mean, a pretty important part of the story right. So maybe you could just give us a flavor for that and then just since I'm. The last question I'll ask as well.

Anything you want to yeah, I would just agree with what Larry said, we saw strong demand for all three products are sort of the virtual and live all V. And we were really pleased with Q2 was really a step up in new patient starts as we said earlier exceed our expectations to Blair's point nothing to look at with inventory inventory is growing with demand right.

Richard Pops: I don't want to front run the World Fleet presentation and ask a specific data question, but taking a step back, there's been a lot of focus, right or wrong, from Wall Street on visual adverse events with the Erexon program. And I guess I wanted to ask the Alkermes team, you know, one, do you think the focus on visual AEs is warranted? Like, are we on the right track in kind of thinking about whether this is clinically significant? And then two, where would you draw the line on, you know, a visual AE signal that is benign and might not have much regulatory commercial consequence versus something that might be more significant and, you know, might require certain things like driving studies or could result in certain restrictions on a drug label?

The working assumption is that insomnia.

It was only seen at the very beginning so should we still have that.

So we're pleased with that.

Great. Thank you.

Function, but any type of it's probably still on the scene in week one thanks.

Thank you.

Our last question comes from line of Marc Goodman with Leerink Partners. Please proceed with your question.

Go ahead, Marcus on the Catholic So, let's clear that up because it's important and I think we haven't really clear picture of this mark sure. We do we do think.

Yes, just back on this cataplexy endpoint discussion like when you talked about the learnings for the phase III. These learnings basically just the statistical methods that you were talking about are you talking about using different assay I'm a little confused maybe you can.

Cataplexy results.

A lot of what we saw likelihood to do with outliers that we saw on the province, one study and we think some of that could have to do with the operational implementation of the assay, so, particularly things like standardization of how patients are recording cataplexy.

Richard Pops: Thanks so much.

She had a little more light there I mean, we're all still a little confused what happened with the cataplexy data I'm wondering like are we even got to learn.

Richard Pops: Good morning, Paul. Hey, let me start, then I'll hand it over to the experts. But I can just tell you, in my experience, dealing both with clinicians and investigators and patient groups, and dealing with Wall Street, the focus is almost entirely on the Wall Street side, on the visual AEs. And it's an important contribution that we made in this particular study, because, as I've said before, there was a reasonable scientific medical question at the beginning of this program about whether orexin 2-receptor agonists can have a direct effect on the eye. So with this rigorous baseline ophthalmic exam at baseline, and then six weeks later, having 90 plus patients worth of data to establish now that we saw no changes was an important step forward in that.

At sites and even across sites in what is a global study. So these are the types of things that for phase III or we're going to apply.

Once we once we see the data in Singapore, we're going to feel much better about it I mean, because you were talking about let's just go significantly.

So what needs to get on the label like doesn't it needs to be stat Sig to get on the label I mean, it's a pretty important part of the story right. So maybe you could just give us a flavor for that and then just since I'm. The last question I'll ask as well.

And attempts to reduce this variability and minimize any outliers that we might see and to your appointment of course, you youll need to see statistically significant results for inclusion in the label and that's that would be our objective and when you see the data at world sleep.

The working assumption is that insomnia.

Only seen at the very beginning so should we still have that.

You can draw your own conclusions about the strength of the signal on cataplexy, which shouldn't be surprising given all of these other endpoints are moving so strongly toward normal you wouldn't expect to see a whole lot of discord and data in a cataplexy, but the statistic itself as you saw on the top line release significantly one dose and not at the other two doses.

Function, but any type of assignment is still on the scene in week one thanks.

Go ahead Marcus on the on the kind of thing so it's clear that up because it's important and I think we haven't really clear picture of this mark sure. We do we do think the <unk>.

Craig Hopkinson: But I think from a clinical perspective, I'll let these guys comment on that and what their experience has been. But we won't provide any more specific AE data on this call, other than what's in the press release, but I think they can give you some qualitative Yeah, exactly. As Rich pointed out, we're not providing additional AE data, but I think in general we do feel that, based on some of our discussions, that any AE that's thought to be mild and not interfering with patients' daily activity is not going to be something that's going to be overly concerning, both for physicians or for their patients.

Cataplexy results.

A lot of what we saw in likelihood to do with outliers that we saw on the <unk>. One study and we think some of that could have to do with the operational implementation of the assay, so, particularly things like standardization of how patients are recording cataplexy.

I think you'll get a little bit more understanding about why that might have happened when you see the variability.

And we're not going to comment on the time course of the various aes youll see youll see more of that at grocery as well.

At sites and even across sites in what is a global study. So these are the types of things that for phase three we're going to apply.

Yeah.

Yeah.

Thank you.

At this time, we've reached the end of the question and answer session I will hand, the floor back to management for closing remarks.

And attempts to reduce this variability and minimize any outliers that we might see and to your appointment of course, you youll need to see statistically significant results for inclusion in the label and that's that would be our objective and when you see the data at World Sleep you can draw your own conclusions about the strength of the signal in cataplexy, which shouldnt be surprising.

Great. Thanks, everyone for joining us on our call today, please don't hesitate to reach out to the company. If you have any follow up questions. Thank you.

Craig Hopkinson: Yeah, and maybe just to add to that, you know, we had a data safety monitoring board in place overseeing all safety from the Vibrance program, and they've met a number of times and given us the green light to proceed. In addition to that, as Richard has pointed out, the ophthalmologic exams were normal, we established baseline, so that gives us some confidence there as well. And then sort of directionally, as we've said, as we've sort of said in our disclosure, the adverse event profile is in line with what we saw across the Phase I healthy volunteer and patient cohorts from that Phase I program.

This will conclude today's conference you may disconnect. Your lines at this time. Thank you for your participation and have a wonderful day.

And all these other endpoints are moving so strongly toward normal you you wouldnt expect to see a whole lot of discord and data in a cataplexy, but the statistic itself as you saw on the top line release significantly one dose and not at the other two doses.

I think you'll get a little bit more understanding about why that might have happened when you see the variability.

And we you know we're not going to comment on the time course of of the various aes youll see youll see more of that proceeds as well.

Richard Pops: Hey, Paul, let me just add, because it might anticipate some other questions that we're going to get. Just as a matter of fact, the safety database is actually not even closed until probably mid-August, because recall, we have a seven-week extension that follows the six-week double-blind. So actually, we couldn't populate data tables with specific numbers until that database is locked. So part of the reason for the level of disclosure at the top line was simply to characterize accurately what we found in the six-week double-blind period.

Yeah.

Yeah.

Thank you.

At this time, we've reached the end of the question and answer session I will hand, the floor back to management for closing remarks.

Great. Thanks, everyone for joining us on our call today, please don't hesitate to reach out to the company. If you have any follow up questions. Thank you.

This will conclude today's conference you may disconnect. Your lines at this time. Thank you for your participation have a wonderful day.

Paul Matteis: We'll actually have very specific data for you by the time we come into world sleep in September. Great. Thanks for all the perspective. You're welcome.

Anastasia: Our next question is in the line of Akash Tiwari with Jeffries. Please proceed with your question. Thanks so much for the question.

Anastasia: This is Anastasia on for Akash. So in phase two, it looked like TOC861 may have left some efficacy on the table on MWT versus 994. How confident are you that 2680 may be able to fully explore that exposure response range between 4 and 8 megs and NT1 and differentiate on efficacy versus Takeda? Yeah, we've always thought that a range of doses would be a competitive advantage. And, you know, I'm not going to comment on the competitive programs. I think that one of the features of this program has always been the ability to dose across a wide range, in NT1 leading into NT2 and IH as well.

Richard Pops: So we'll wait to see the data from the NT2 and IH cohorts, but we're very pleased with the dose range that we selected for this NT1 study.

Andrea Newkirk: The next question is in the line of Andrea Newkirk with Goldman Sachs. Please proceed with your question. Good morning. Thanks for taking the question.

Andrea Newkirk: Rich, I was just wondering if you might be willing to speak a little bit about how you're thinking about the regulatory path from here, recognizing you do still need to meet with the FDA. But is there the possibility that these vibrant studies could serve as registrational trials? And if not, would you expect one registration enabling trial per indication would be sufficient to support approval or would you need to for each?

Richard Pops: Good morning, Andrea. Thank you for the question. Yeah, I think, okay, the first stipulation will be that FDA is a fairly fluid place right now, but I'm going to answer the question based on what we know coming into things, and that is that our expectation was to complete the NT2 study, and because we'll be seeking a label that encompasses narcolepsy writ large, which would encompass NT1 and NT2, we would wait for those data from NT2 before scheduling our formal end of Phase 2 meeting with FDA, where we'll agree on the Phase 3 design. The reason we're doing that is because we're currently the only player in NT2 at this late stage, and so that's a very differentiating part of the product and potentially the label, and as we understand the NT2 doses relative to the NT1 doses, then we'll have the ability to sit down with the FDA and map out the Phase 3 program.

Andrea Newkirk: Our assumption right now is that our Phase 3 program will look very similar to the competitors, i.e., a three-month study in NT1 and probably a similar study in NT2, one each, but we would confirm that in our end of Phase 2 meeting. Okay, thank you.

Umer Raffat: The next question is from the line of Umer Raffat with Evercore ISI. Please proceed with your question. Hi guys, thanks for taking my question. Just two quick ones. One, could you confirm the dose response is in fact linear on MWT? And I ask because there's been some questions around the cataplexy observation. And my question is, I realize there's a numerical trend, but it's not stat sig at eight milligrams. Is it reasonable to assume, based on how the data and the variability looked, that you guys tripped the threshold on Poisson and ended up using negative binomial distribution to drive the p-value?

Umer Raffat: And did that explain partially why p-value was broader for eight milligrams?

Umer Raffat: Thank you.

Richard Pops: Good morning Umer and Trish. We haven't talked anything specifically about the linearity or lack thereof of the dose response. You'll actually see all the by dose information in just a few weeks time at World Sleep. Your statistical question on cataplexy is impossible for me to answer so I'll pass it to the pros. Sure, yes, I can answer that. So we did use the negative binomial analysis, and that was actually pre-specified for us in conjunction with discussions with the FDA. So we did use that analysis and pre-specify it, and based on our data, that was the appropriate analysis.

Marcus Yance: So, can I just clarify then, Poisson was not your base case? It went straight into negative binomial? That's correct. Wouldn't that create a discrepancy when we look at p-values for Takeda dataset versus Alkermes dataset? There wouldn't be apples to apples on p-value basis. Yeah, no, it's a good question. I mean, we're not comparing apples to apples directly with their data set regardless. Obviously, they were different patient populations, so we wouldn't compare across trials directly. But this is the analysis that we used in a pre-specified manner. And I would say, Umer, that's one statistic that you use as a lens to look at the data.

Richard Pops: When you go to world sleep, you'll see other perspectives on that data that I think very clearly show elixirexin's effect on cataplexy at these doses. So for us, we think of it as more of a methodological learning for phase three, which statistic and which method are we going to apply in phase three, recognizing we see a very clear cataplexy signal.

Richard Pops: Got it. And Richard, I'm sorry. Since this is so important, I just want to be clear. Numerical trend-wise, you think the data is as competitive as Takeda on cataplexy? Well, again, it's apples and oranges. So you can make the decision yourself when you see the data itself, but I think we feel quite comfortable that we have a clear cataplexy signal that you'll see. There's some outlier data that really confuses the statistic. So you can try to correct for that using various statistical methods, or you can just look at the data, and you'll see the data in more complete revelation at world sleep.

Richard Pops: And I can talk about that afterwards, but I think you'd be satisfied that we have a very clear signal on cataplexy. Just as an aside, without math associated with it, remember the narcolepsy severity scale picks up cataplexy as one of its key domains, and we've normalized patients on the NSS. So all the data tended to work complementary.

Jessica Fye: Thank you.

Adam: Our next question comes from the line of Jessica Fye with J.P. Morgan. Please use your question.

Adam: Hello, this is Adam on for Jess. Thank you for taking our question. I just wanted to ask the Alexa Exitens, could you please remind us of the potency selectivity towards the OX2R over the OX1R? Thank you.

Adam: Adam, I thought you were going to ask how to pronounce Elixirexon, because it's not the easiest word to pronounce. Yes, 5,000 folks. So it's 5,000 fold more. Great, thank you.

Joseph Tome: Our next question is from the line of Joseph Tome, West TD Count. Please receive your question. Hi there. Good morning. Congrats on the progress, and thank you for taking my question. Maybe when we do look at the full safety profile of Alexarexin, maybe how much of that can be extrapolated to some of your follow-on compounds, 4510 and 7290? It looks like there's obviously some class Arexin side effects that we're seeing, but is there anything different about the targeting or the dosing of 4510, 7290, that you think could result in a different AE profile, or I guess how much will the Alexarexin initial data de-risk follow-on?

Marcus Yance: Obviously, we need to see the data, but how are you thinking about translatability there? Go ahead. We think, you know, yes, they're working on the same receptor. So we do think there will be some similarities.

Marcus Yance: That being said, the molecules were purposely developed to have different pharmacokinetic profiles and different structures that could lead them to not all look exactly the same on an AE profile. So, of course, the human data will answer that question for us completely. And we hope to have that for you in the near future on both 4510 and 7290.

Richard Pops: And, Joe, if you don't mind, let me build on your question to anticipate questions we've been getting from investors. And that is, how do the NT1 data anticipate what we've seen in NT2? And I think I just want to make clear our original hypothesis, which has been confirmed by our own data, which is we believe that there's actually a frame shift in terms of the tolerability and sensitivity as you move from NT1 to NT2, meaning you'll need higher doses to drive efficacy and you'll need higher doses to drive the on-target side effects as well. So we imagine just the dose response curve shifting to the right in that.

Richard Pops: And that's what is consistent with the data we saw in our Phase 1B study. We'll know more definitively, obviously, when we get those data, but that's the pretest hypothesis. All right.

Richard Pops: Thank you.

Unknown Executive: The next question is from the line of Uy Ear with Missouho Security. Please issue your question. Guys, yeah, thanks for taking our question. Given that the NT2 study, I guess the primary endpoint is complete, expects to complete in August, just wondering, is there a good chance that you also present the NT2 data at WorldSleep? Thank you.

Unknown Executive: We just be clear. So we should complete enrollment in the next couple of weeks, which then with a two week with a two month primary analysis puts us into the fall. So there won't be any NT2 data at World's League. There'll be plenty of NT1 to review. So you won't you won't be hungry. Thank you.

David Amsellem: The next questions are from the line of David Amsellem with Piper Sandler. Please just use your questions. Hey, thanks.

David Amsellem: So, number one, are you planning to build in dosing flexibility or any sort of titration in the phase three as a means of minimizing treatment emergent adverse events? And then secondly, this is a commercial question. It's not, of course, unheard of to have a wakefulness promoting agent that does not have cataplexy in the label. I guess my question here is just given the wakefulness promoting properties of elixirextin, how important is it to have cataplexy in the label in terms of a commercial adoption perspective?

David Amsellem: Thank you.

David Amsellem: So good morning, David. I'll give you my view and then I'll hand it over to the guys. We haven't made the call yet on the phase three dosing because we haven't finished all the analyses and we also want to see the NT2 dosing data before we decide on the range of doses. So stay tuned there. We have a, what's so exciting about running phase twos of this quality is that now we have 92 patients worth of data to model. And our view is that that level of exposure time and is essential for actually making those dosimetry decisions for the registrational program.

Todd Nichols: So stay tuned on that. Wakefulness, my own view, and Todd can answer the question, is that we believe elixirexin is going to have a cataplexy claim in the label because the signal is quite clear. So it's more a matter of tuning the assay to make sure that we can see that in the data. But Todd, you can comment on whether you think cataplexy is an important part of the presentation. I agree, I think you captured it.

Todd Nichols: All right, thanks.

David Hoang: The next question is from the line of David Hoang with Deutsche Bank. Please proceed with your question. Hi, congrats on the quarter and taking my question. So I just wanted to ask about the upper dose in the NT2 and IH studies.

Craig Hopkinson: I believe it's 18 milligrams. Could you just remind us how you landed on 18, specifically given 25 was used in the earlier phase 1B, and what would be, I guess, the ideal number to take forward into phase 3? Thank you.

Craig Hopkinson: Craig, you want to talk about this? Yeah, so we employed some sophisticated modeling, basically taking into account all the data that we had collected from our Healthy Volunteer Studies as well as our Phase 1B program, and ultimately modeled out the doses for Phase 2, and that's how we came to the dose selection. Thank you.

Amit Fabia: The next question is from the line of Amit Fabia with Needham & Company. Good morning. Thanks for taking my question.

Richard Pops: Going back to the focus on visual AEs, can you give us sort of your high-level view on how important is it to avoid a dose that might have such an AE even if it were to be transient? and you know would you choose to take a dose into phase three that might have seen a transient visual adverse event and just separately speaking do you think that that is an on-target effect of this class? and, you know.

Richard Pops: As you think about sort of your next-gen assets, do you think that it's just a broadly an on-target effect, or is it more specific to the structure of a given drug? Thank you.

Marcus Yance: Let me start out, Ami. I'm just going to try to pull you back up from the visual AE obsession to the question on AEs in general. I mean, what we're looking at in this data set is doses where we know there are on-target AEs, namely, you know, insomnia and polyuria, that we and others have observed as on-target effects that could be, that would limit your dose. So I think the virtue of this program is we've run three different doses for six-week periods of time in the outpatient setting, and we'll get a complete time course as well as severity map of those AEs.

Marcus Yance: And we have so much more data to look at together, because let's say, for example, if you have a numerical AE, Did it happen every day over the 42 doses, or did it happen once in the first week and then went away? You know, there's a lot of nuance to this, so I don't think it's easy to answer the question about what doses we would take forward, because I think that there's a range of different AEs that we're going to be focusing on, and we think our competitive advantage is going to be this range of doses, because not all patients are the same, and people react to different doses, and I think that that would be true for efficacy as well as for AEs.

Marcus Yance: Marcus, I'm happy to hear your view on this. Yes, yeah, I would agree. We're, as we speak, doing complicated modeling on exposure response, exposure safety analyses, and that's going to encompass everything we've seen. We're looking at this data in every way we can to help us determine what the best range of doses is going to be to move forward into Phase 3, and so that's going to encompass efficacy, it's going to encompass safety, and, you know, even ease of dosing, and so we're thinking about all possible criteria when we think about dosing moving forward. Thank you.

Ash Verma: The next question is in the line of Ash Verma with UBS. Hi, thanks for taking my question. So just on these like phase 2 studies, like what time of the day are patients dozed with 2680 and the sinus down in the outpatient setting, except for the MWT days, but just what's your direction to the patients?

Marcus Yance: And then secondly, on the visual disturbance that you mentioned, so the PR says that you're not seeing any signal. But is that statement based on AEs that you may have seen in and outside of the scheduled exams?

Marcus Yance: I can answer the first part. So we tell them generally to take it in the morning, so roughly around 8 a.m. There's of course a window around that just to accommodate for various lifestyles. But roughly 8 a.m. in the morning is when we ask them to take it. And we didn't delay any specific AE table elements until the phase one, I'm sorry, until the phase two safety database is closed in mid-August. So you'll see those data at WorldSleep.

Marcus Yance: Thank you.

Leonid Timashev: The next question is in the line of Leonid Timashev with RBC Capital Markets. Please receive your question. Thanks, guys.

Richard Pops: I just want to ask on the endpoints, just given what you've seen out of Vibrance 1, are you still thinking that MWT is the best way to go forward compared to ESS and both for, as you think about, I guess, the dual design for Vibrance 2 and then the ESS focus for Vibrance 3? And then related to that, given all the secondaries that you hit on, including some of the exploratories, how are you thinking about elevating some of those exploratory endpoints to secondaries or key secondaries for a Phase 3 program like Cognition or Fatigue? And would you try to aim to get those on the label?

Richard Pops: Thanks. So, you know, from our perspective, we believe both MWT and Epworth are really important measures. MWT, obviously, the more objective measure, Epworth really sort of expressing the patient's sort of subjective assessment. The reason that we elevated Epworth to a dual primary in the NT2 study is because of our sort of thought process around planning for regulatory interactions, really taking a look at the late stage clinical trial landscape, and planning for our Phase 3 program. So, yes, we believe both are important, and I think the data from the NT2 study will help us plan for our Phase 3 program with the dual primary in place.

Marcus Yance: And on the key secondaries, Marcus, you might want to comment on, but from my perspective, these were really exploratory. Some of these scales, I don't think, have been used in narcolepsy studies at all. And so we were curious to see whether we would see movement. And boy, did we. I mean, we really saw clear signals. And you'll see more of those data at World Sleep.

Marcus Yance: Given the magnitude of the response and how clear it was, I think we have to do a lot of thinking now about how we might elevate those in the hierarchy, but please comment on that. Exactly right, Rich. And the team's here working diligently to look at exactly that, all of these various exploratory outcomes, the ones where we succeeded that, again, were hypotheses that we've now shown significant data on. And so the team is really working on how do we pull these in through the phase three and elevate them into the key secondary realm in a way that allows us to really test the aspects of this drug more thoroughly.

Jason Gerberry: Thank you.

Jason Gerberry: The next question comes from the line of Jason Gerberry with Bank of America. Hey, guys. Good morning. Thanks for taking my question.

Jason Gerberry: So maybe just wanted to probe a little bit, just your understanding of the relationship of PK and the weekly cataplexy endpoint, and whether or not you feel comfortable enough to rule out QD versus BID approaches conferring, you know, any advantage in terms of the WCR measurement. And then also just, I know you're not commenting on phase 3 dosing plans yet, wanting to see the NT2 results first, but I'm wondering if we can take from your comments that at least in the context of NT1, that there's at least enough confidence in the TOCS profile of the high 8MG dose that you could potentially push dose in future NT1 pivotal.

Marcus Yance: Thanks.

Marcus Yance: Hey, you guys want to talk about the PK-WCR relationship? Sure. I mean, at this point, those analyses are ongoing. So we've reported, as you know, sort of the top-line results, and we're really digging deeper into the PK, again, as I mentioned, sort of exposure, exposure response, exposure safety. So that's going to be coming soon and potentially something you'll see in the future. But is it fair to say, Marc, I don't think there's a QD versus BID difference that we think is... We don't know, that's right. And with respect to the phase 3 dosing plans, I mean, yeah, I mean, at this point for phase 3 dosing, again, we're still, we're still making those determinations.

Marcus Yance: So it's hard to speak to them. We do have confidence fully in our tox profile at 8 milligrams. So there's, there's no concern there. And we're, we're obviously taking that into account as well as everything else we've talked about to determine our Got it, thank you.

Luke Herman: The next question is from the line of Luke Herman with Baird. Let's just use your question.

Blair Jackson: Luke, do we have you? Oh, sorry, I was on mute. Sorry, just a quick one for me. It looks like some nice step ups in revenues across the board. Can you just talk about the relative contribution from inventory or seasonal dynamics as compared to underlying demand for the commercial portfolio? Thank you.

Blair Jackson: Yeah, this is Blair. I'll start with on the number basis and I'll turn it over to Todd to get in some detail. I think number one, as you look at our proprietary programs, we saw a demand increase across all three programs over the time period. We actually didn't have any inventory dynamics that contributed to this quarter. And so this is in line with normal seasonal dynamics and a contribution of our strong commercial performance.

Todd Nichols: Todd, anything you want to add? Yeah, I would just agree with what Blair said. We saw strong demand for all three products. Aristotle, Vivitrol, and Livolvi. And we were really pleased with Q2, was really to step up a new patient starts. As we said earlier, exceed our expectations. To Blair's point, nothing to look at with inventory. Inventories is growing with demand right now. So we'll.

Unknown Executive: Great, thank you. Thank you.

Mark Goodman: Our last question comes from the line of Mark Goodman with Lear Inc. Partners. Please use your question.

Mark Goodman: Yeah, just back on this cataplexy endpoint discussion, like when you talked about the learnings for the phase three, are these learnings basically just the statistical methods that you were talking about, or are you talking about using different assays? I'm a little confused. Maybe you can shine a little more light there. I mean, we're all still a little confused what happened with the cataplexy data. And we're wondering, like, are we even going to learn? Like, once we see the data in Singapore, we're going to feel much better about it. I mean, because you were talking about statistical significance and what needs to get on the label.

Mark Goodman: Like, doesn't it need to be statistic to get on the label? I mean, it's a pretty important part of the story, right? So, maybe you could just give us a flavor for that.

Marcus Yance: And then, just since I'm the last question I'll ask as well, the working assumption is that insomnia is only seen at the very beginning. So, should we still have that assumption that, you know, any type of insomnia is still only seen in week one? Thanks.

Marcus Yance: Go ahead, Marcus, on the cataplexy. Let's clear that up, because it's important, and I think we have a really clear picture of this, Mark. Sure, we do. We do think the cataplexy results have a lot of what we saw likely had to do with outliers that we saw in the Vibrance I study, and we think some of that could have to do with the operational implementation of the assay, so particularly things like standardization of how patients are recording cataplexy at sites and even across sites in what is a global study. So these are the types of things that, for Phase 3, we're going to apply in attempts to reduce this variability and minimize any outliers.

Marcus Yance: And to your point, of course, you'll need to see statistically significant results for an inclusion in the label, and that would be our objective. And when you see the data at World Sleep, I think you can draw your own conclusions about the strength of the signal on cataplexy, which shouldn't be surprising, given all these other endpoints are moving so strongly toward normal. You wouldn't expect to see a whole lot of discordant data in a cataplexy, but the statistic itself, as you saw in the top-line release, you know, significant at one dose and not at the other two doses, I think you'll get a little bit more understanding about why that might have happened when you see the variability.

Marcus Yance: And, you know, we're not going to comment on the time course of the various AEs. You'll see you'll see more of that at GroveSleep as well. Thank.

Unknown Executive: At this time, we've reached the end of the question and answer session, and I'll hand the floor back to management for closing remarks. Thanks everyone for joining us on the call today. Please don't hesitate to reach out to the company if you have any follow-up questions.

Unknown Executive: Thank you. This will conclude today's conference. I'm going to disconnect your lines at this time.

Unknown Executive: Thank you for your participation and have a wonderful day.