Alkermes plc

Greetings, and welcome to the Alkermes First Quarter 2023 Financial Results Conference Call. My name is Rob, and I'll be your operator for today's call. 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 on 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 begin.

Thank you. Good morning. Welcome to the Alchemist PLC conference call to discuss our financial results and business update for the quarter ended March 31, 2023. With me today are Richard Pops, our CEO, Ian Brown, our CFO, and Todd Nichols, our Chief Commercial Officer. Before we begin, I encourage everyone to go to the investor section of Alchemist.com to find our press release, related financial tables, and reconciliations of the gap to non-gap financial measures that we'll discuss today. We believe the non-GAAP financial results in conjunction with the GAAP results are useful in understanding the ongoing economics of our business. 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 expressed 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 developments. After our prepared remarks, we'll open the call for Q&A, and now I'll turn the call over to Rich.

Thank you, Sandy. Good morning, everyone. We have a number of important and positive updates to go through today, so I'm going to get right into it. I'm going to start with a brief update on the announcement we made yesterday related to our arbitration with Janssen. I'm then going to hand it to Ian for a review of the financial results for the quarter, and then to Todd for an overview of our commercial products. I'll come back then and close with an update on the progress we're making on the separation of the oncology business and our ALX2680 orexin program. So regarding the arbitration with Janssen, recall that this pertains to royalties in the U.S. sales of three long-acting Invega franchise products, Invega Sustena, Invega Trinza, and Invega Half-Era. which are antipsychotic medications, as well as Cabinuva, which is an HIV product. In January, we announced that the tribunal, which is a panel of three experienced arbitrators, issued an interim award in which it agreed unanimously with Alkermes on the central issue of the arbitration, which is that while Janssen had the right to terminate the license agreements, it may not continue to sell the products developed under those agreements without paying royalties to Alkermes. Last week, we received the second favorable interim award from the panel, which addressed the outstanding economic issues. First, for 2022, we are due back royalties of approximately $194 million. Second, related to 2023 and beyond, the award provides that a separate royalty term applies for each of Envega Sustena, Envega Trinza, and Envega Jafira. For Envega Sustena, we would be owed royalties through August 20th, 24, which is consistent with our previous expectations. However, for both In Vega Trinza and In Vega Hapiera, the panel agreed with our position that the royalty term extends beyond 2024, through the second quarter of 2030. This would represent an additional six years of royalty revenues for these two medicines. In addition, the award provides that royalties for CABANUVA in the US are owed through the end of 2036. So to summarize, Once final, this would result in payment for back royalties due, reinstatement of royalties going forward, and royalty terms for Invega Trinza, Invega Half-Era, and Cabanuva into the 2030s. This represents significant potential economic upside and provides strategic capital to the balance sheet and additional long-term contributors to our P&L. In terms of the next steps, the panel directed the parties to confer and advise within 21 days as to whether either party believes that any issues remain for resolution by the panel prior to issuance of a final award. We are gratified by this latest interim award in support of our position, and we'll look forward to the final award and resolution of this matter. So with that, I'm going to pass it to Ian for an overview of the quarter, and then to Todd. Go ahead, Ian.

Great. Thank you, Rich, and hello, everyone. I'm happy to report solid financial results for the first quarter, driven by the strength of our proprietary commercial product portfolio. our continued focus on operating efficiency, and the commercial leverage we have built into our business. We are confident that we can continue to build on this momentum as we look ahead through the remainder of 2023. As Rich mentioned, the anticipated outcome of the Janssen arbitration, once final, represents significant potential upside to our current financial expectations for 2023 and our long-term profitability targets for 2024 and 2025. However, we will wait until we have further resolution of the dispute before revising any current or future financial expectations. In the meantime, today, based on the performance of our core business and as we've continued to execute across our strategic priorities, we are reiterating our financial expectations for 2023, which were detailed in our press release and AK filed on February the 16th. Now, for the first quarter, we generated total revenues of $287.6 million, driven primarily by our proprietary product portfolio, which grew 25% year over year. Starting with Vivitrol, net sales in the quarter were $96.7 million, reflecting 14% growth year over year, driven primarily by the alcohol dependence indication. Inventory in the channel was fairly stable, and gross-to-net deductions were within normal ranges for the quarter. For the full year, we continue to expect Vivitrol net sales in the range of $380 to $410 million. Moving on to the Aristada product family, for the quarter, Aristada net sales increased 10% year-over-year to $80.1 million, primarily driven by underlying prescription growth of 10% on a months of therapy basis. Inventory in the channel and growth net adjustments were relatively stable for the quarter. And for the full year, we continue to expect Aristada net sales in the range of $315 to $345 million. LaVolvi net sales for the quarter were $38 million, up 9% sequentially. Underlying prescription growth was 16%. End market demand grew at a faster pace than inventory in the channel, which explains the difference between these two growth rates. Growth to net adjustments in Q1 were 26.4%, primarily reflecting a continuation of our disciplined contracting strategy in the commercial space. We continue to anticipate that growth to net adjustments will remain fairly stable in the high 20% range during the first half of the year, and then may increase in the second half if we determine there's a benefit to contracting in the commercial channel. For the full year, we continue to expect Le Balvinet sales in the range of $180 to $205 million, driven primarily by strong underlying demand. Moving on to our manufacturing and royalty business, in the first quarter, we recorded manufacturing and royalty revenues of $72.9 million, compared to $105.2 million in the same period in the prior year. Royalties from sales of the Long-Acting and Vega products were $13.6 million, compared to $37.1 million for the first quarter of 2022. This decrease was driven primarily by Janssen's partial termination of the agreement related to royalties on sales of these products in the United States, which is a subject of our ongoing arbitration with Janssen. Revenues from Vumerity were $28.9 million compared to $30.6 million in the same period in the prior year. And this decrease reflects a reduction in Biogen's end market and ex-sales of the product. Turning to expenses, total operating expenses were $335.1 million for the first quarter compared to $305.1 million in the same period in the prior year. R&D expenses for the first quarter decreased to $93.6 million, compared to $96 million for the same period in the prior year, reflecting focused investments in the Nembalucan Clinical Program, Levolvi Lifecycle Management Studies, and our Orexin-2 Receptor Agonist Program. SG&A expenses increased to $174.5 million, from $145.1 million for the same period in the prior year, reflecting continued investment in the launch of Levolvi, including the start of the digital direct-to-consumer campaign, in addition to certain expenses related to the separation of the oncology business. Our top-line results, combined with our continued focus on disciplined operating expense management, resulted in a gap net loss of approximately $41.8 million and non-gap net income of approximately $2.4 million for the quarter. Turning to our balance sheet, we ended the first quarter with approximately $692.5 million in cash and total investments, and with total debt outstanding of approximately $292.6 million, we had a positive net cash position of approximately $400 million. As Rich noted earlier, a favorable resolution of the Janssen arbitration would further strengthen our balance sheet. Now today we're reiterating our financial expectations for 2023 based on the solid performance of our commercial products and our continued focus on operational efficiencies. As a reminder, our financial expectations reflect the combined neuroscience and oncology business for the full year as we work toward the planned separation, which we currently expect to complete in the second half of the year. And as I mentioned earlier, our financial expectations for 2023 do not yet reflect the potential upside that favorable resolution of the Anson arbitration is expected to provide. By way of a framework, I would expect to record the back royalties related to 2022 of $194 million, inclusive of interest, as a lump sum, which would be adjusted out of our non-GAAP net income measure due to the one-time nature of that anticipated payment. Separately, for royalties earned related to 2023 net sales of the Long-Acting and Vega products, we would expect to record these as royalty revenues in the normal course. We estimate that this could be in the ballpark of approximately $250 million of incremental royalty revenue worldwide over and above our current financial expectations for 2023 and would flow through to both the GAAP and non-GAAP bottom line. Taking a step back, over the past several years, the company's done significant work to drive operational efficiency and calibrate our cost structure to appropriately support the company's strategic priorities and growth opportunities. Looking ahead, we believe that our core business is well positioned to achieve our current full year 2023 guidance, as well as the accelerated profitability targets we announced earlier this year. As we plan for the separation of the oncology business, We will maintain our focus on the strength and potential of the neuroscience business, which is characterized by its financial profile, the quality of its commercial portfolio, and its potential for enhanced profitability and long-term growth. And with that, I'll hand the call over to Todd. Great.

Thank you, Ian. And good morning, everyone. I'm pleased to share that we delivered strong growth across our proprietary commercial portfolio in the first quarter, building off the momentum we generated in 2022. Net sales from the portfolio increased 25% year-over-year and were driven by double-digit growth for each of our three brands, Vivitrol, Aristata, and Levolvi. We are particularly pleased with the strong continued uptake of Levolvi in the oral anti-psychotic market. So let's start there. During the quarter, Lebalvi net sales were $38 million. Total prescriptions grew 16% sequentially to approximately 33,000 TRXs for the first quarter. As of the end of the first quarter, nearly 24,000 patients have been treated with Lebalvi since launch. At this stage of the launch, our focus continues to be on expanding prescriber breadth, which grew by 1,700 prescribers to approximately 9,300 healthcare providers who have written a prescription since launch. As we outlined earlier this year, our strategy for Le Balvie in 2023 is focused on three key initiatives, growing prescriber breadth, further leveraging our access profile, and building awareness for Le Balvie. Our direct-to-consumer campaign will be a key factor in accomplishing these goals. DTC campaigns have been shown to be highly effective in driving brand growth in many therapeutic areas, particularly in psychiatry, where market research and prescribing patterns suggest that when patients request a specific brand from their healthcare provider, there is a high likelihood they will be prescribed the brand requested. Our DTC strategy is grounded in deep patient and healthcare provider insights, including immediate consumption habits, as well as the significant opportunity and unmet need in schizophrenia and bipolar I disorder. Our goal is to drive awareness and uptake for LaVolvi through execution of a broad, differentiated campaign across multiple media channels, including digital and TV. The digital portion of the campaign was initiated earlier this year and is highly targeted based on the media consumption patterns of people with bipolar I disorder and schizophrenia. Early returns from our digital campaign have been encouraging, as evidenced by quantitative increases in website traffic, consumer engagement, and brand awareness. The TV component of our DTC program will launch next week and will be focused on Bipolar I disorder. The campaign is designed to drive high levels of awareness among patients, caregivers, and healthcare providers. Market access continues to play an important role for LaVolvi like all brands in the space. In Medicare and Medicaid, we currently have a pathway to access for all patients. On the commercial side, we have established a solid foundation. Looking ahead, we may look to strategically contract in the commercial space, balancing volume and the profitability of each unit. We believe Levolvi is on a strong trajectory and look forward to sharing our progress with you. Turning to the Aristotle product family. Net sales in the first quarter were $80.1 million, driven by TRX growth of approximately 10% year-over-year on a month-of-therapy basis. This performance was driven by Aristata's differentiated value proposition, including its once-every-two-month dosing option, and the Aristata initiation regimen, both of which are supported by clinical data from our Alpine study. We are seeing encouraging signs of a continued market recovery for LAIs, and believe that we are well-positioned to continue to drive growth for the brand. Aristata and Levolvi represent important treatment options designed to address the real-world challenges patients face and supported by proven clinical efficacy. We believe this differentiated psychiatric portfolio together with our specialized commercial capabilities distinguishes Alkermes among healthcare providers, treatment systems, and payers and offers a platform for potential future growth. Turning to Vivitrol, net sales in the first quarter increased 14% year-over-year to $96.7 million. The alcohol dependence indication continues to be an important driver of growth and accounts for approximately 65% of the Vivitrol volume. Importantly, prescriber breadth for Vivitrol has continued to expand within the alcohol dependence indication, which has driven new patient starts over recent quarters. The trial in our Vivitrol and the litigation with TAVA took place in February. and a decision is expected in the second half of the year. We remain confident in the innovation embodied in Vivitrol. Regardless of the outcome of this litigation, we believe the nature of the product and the complexities and dynamics of the market in which it is commercialized make typical generic erosion unlikely. Overall, we are very pleased with the performance of our commercial product portfolio in the first quarter and believe we are well positioned to achieve the goals we outline for the year ahead. We look forward to updating you on our progress throughout the year. And with that, I'll hand the call over to Rich.

That's great. Thank you, Todd. So at the beginning of the year, we outlined three strategic priorities, driving the ongoing launch of Levolvi, advancing our orexin program in narcolepsy and other hypersomnia conditions, and executing on the planned separation of our oncology business. Four months in, we're advancing on all three and believe that we can drive significant value for shareholders. As you just heard from Todd, we're executing our strategy for Levalvi, and we've established a strong platform for growth. Levalvi clearly demonstrates the power of alchemy science and the opportunity to leverage our commercial capabilities. I'm going to focus now on where we stand with the separation of the oncology business and the ALX2680 orexin program. We believe the separation of the oncology business will reveal the value of our neuroscience business, which has come more clearly into focus with the launch of Levalvi, and at the same time, provide shareholders and investors with an independent and more direct opportunity to realize value from the oncology investments that we've made. The separation is expected to yield a number of benefits for each business, including driving a sharp strategic focus, simplifying capital allocation decision-making, and increasing each business's flexibility to pursue growth and investment strategies more directly aligned with their respective goals. We've made significant progress in the quarter toward launching what would become a new independent public company named Mural Oncology PLC. Last week, we announced that we submitted a confidential draft Form 10 registration statement with the SEC. In addition, we recently submitted a request for a private letter ruling to the IRS to support the separation as a tax-free distribution to Alkermes shareholders for U.S. federal income tax purposes. Submission of the Form 10 and the PLR request represent two labor-intensive and long lead time work streams in support of the separation. With these two initial submissions now in the review phase, we believe we'll be well positioned to complete the separation later this year as expected, subject to customary conditions, including final approval from our board of directors. We're also advanced in our process to identify and recruit senior management to lead mural oncology. We're pleased with the high caliber of candidates interested in the opportunity, and we'll look forward to sharing updates with you about the CEO role and other key leadership positions as they develop. As a standalone company, we expect Mural Oncology will be an attractive investment anchored by the potential of Nimvalucan, our novel investigational engineered IL-2 variant that is a potential first-in-class cancer immunotherapy. Nimvalucan is the most advanced IL-2 variant in development and is distinguished by data generated in the clinic showing anti-tumor activity as single-agent monotherapy and in combination with checkpoint inhibitors. In addition, mural oncology would have a pipeline of preclinical immunotherapy candidates, our engineered tumor target IL-12 and engineered IL-18 programs, both of which have been advancing preclinical development and represent attractive oncology targets. With a late-stage asset and the potential to be the first in class medicine, preclinical pipeline assets and clear developmental milestones ahead, we believe the separation of the oncology business represents an attractive opportunity for oncology-focused investors. So shifting the focus back to Alkermes, following the planned separation, we expect Alkermes to become a profitable, pure-play neuroscience company with a clear and compelling investment thesis. The Balvis launch success demonstrates our ability to leverage our commercial capabilities in complex addiction and psychiatry markets. With a strong top line, driven by the growth of our proprietary products, a specialized commercial infrastructure, and proven drug development capabilities, the standalone neuroscience business would represent a significant opportunity to capture operating leverage, drive growth and profitability, and advance new potential medicines for neurological disorders. So on that final point, let's spend some time on the erection programs. We're certainly aware of the intense investor interest in this area, so I'm going to give you a bit more detail than we might usually for a Phase I program. Our lead molecule is called ALX2680. It's a small molecule orexin-2 receptor agonist designed as a once-daily oral tablet for the treatment of narcolepsy. During the quarter, our team made important progress in the ongoing Phase I clinical trial. With compounds of this type, early clinical data is highly informative. which is why we've structured the Phase I program with several components, a single ascending dose study followed by a multiple ascending dose study in healthy volunteers, and a Phase I proof of concept study in patients. Structured this way, we can expeditiously cross multiple stage gates related to single and multiple dose safety and tolerability, pharmacokinetics, and pharmacodynamics early in the program. To date, we've successfully advanced our single ascending dose study to doses that exceed our expected therapeutic dose range. In the multiple ascending dose study, we've now cleared sufficient dose levels, which we believed will be therapeutically relevant in narcolepsy, to trigger the initiation of the Phase 1B proof-of-concept cohort in patients. In our single ascending dose work, all doses were well tolerated, and we did not observe any dose-limiting toxicities. In addition to these early indicators of tolerability, the pharmacokinetic profile of ALKS-2680 has been consistent with our modeling, which is encouraging and important given the desired time course of therapeutic effect with a goal of promoting wakefulness during the day and sleep consolidation at night. In the multiple ascending dose study, healthy volunteers are receiving once daily dosing of ALKS-2680 for 10 days. The primary objective of the study is to further elaborate the safety and tolerability of profile of 2680, as well as to collect additional pharmacokinetic and pharmacodynamic data, and this study's proceeding is planned. Taken together, data from the single and multiple ascending dose cohorts have provided initial confirmation of ALK's 2680's PK profile, its dose response, and potency, and provide encouraging signals that it's driving central activity based on EEG and other clinical signs. These data are highly informative and allow us to streamline the design of the next critical phase of the development program, which is getting the drug into patients with narcolepsy. The proof-of-concept study will evaluate established clinical efficacy endpoints, including EEG-based maintenance of wakefulness tests in patients with narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. In a crossover design, subjects will act as their own control and receive single doses of multiple dose levels, as well as a placebo, with a washout period in between. With a small number of subjects per cohort, we believe this approach will allow us to efficiently assess dose response and inform dose ranges for potential future clinical studies. We're poised to commence subject enrollment in this cohort in the coming weeks, following clearance from Ethics Committee, and continue to expect data from this Phase 1b later this year. The market opportunity, the strong biological relevance of the erection pathway, the early target validation work done across the space, all these underpin the high level of excitement surrounding the erection agonist class, both in the treatment community as well as among investors. We'll continue to focus on careful execution while expeditiously advancing this program. I'm going to end there. This is an exciting time at the company. We believe that the business is on the right track to create significant value for shareholders. We're confident in our strategy, and we'll remain sharply focused on executing on our strategic priorities. I'll look forward to sharing continued progress with you over the course of the year. So with that, I'll turn it back to Sandy to run the Q&A.

Thank you. We'll open the call for Q&A now, please.

Thank you, Sandy. At this time, we'll now be conducting a question and answer session. If you'd like to ask a question today, please 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 would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. So that we may address questions from as many participants as possible, we ask that you please limit yourself to one question and one follow-up. One moment, please, while we poll for questions. Thank you. Thank you, and our first question is from the line of Akash Tiwari with Jefferies. Please proceed with your question.

Hey, thanks so much. So on the orexin, your math study started in SPAD. Can you go over how many dosing cohorts you've tested at this point from an exposure perspective? And if you've crossed levels that you think are therapeutically efficacious in narcolepsy and IH, and have you seen any evidence of metabolite accumulation at this point? And just on Levaldi, you grew 16% quarter per quarter on TRX, but sales grew 9%. Heading into Q2, consensus is baking in 19% sales growth. Does that seem doable given growth units are likely set to worsen as we get deeper into 2023? Thank you.

Good morning, Akash. It's Rich. I'll start, then I'll hand it to Todd. The orexin program, as you can tell from my earlier remarks, is really rolling now. I'm not going to give specific information on the various dose levels other than to say that I think the program now encompasses over 60 subjects. and between the SAD and the MAD, and we are above doses that we think are therapeutically relevant for narcolepsy. And that's encouraging. That's why we're really pleased to see the PK, dose proportionality, tolerability, all those things. With respect to the metabolite profile, it says, as we would have anticipated, we've been able to characterize the principal metabolites, and we feel comfortable with where we are with that.

Yeah, and I'll just... I'll just pick up on LaVolvi as well. The first thing is we're not going to guide on the quarter for Q2, but what I would say is that we are really pleased with the uptake of LaVolvi. New patient starts, new prescriptions, TRXs. As we said on the call, TRXs grew 16% quarter over quarter. We really believe that's a result of strong demand growth based on our expanding prescriber universe. which is growing quarter over quarter, and it's very supportive of the market research that we hear from ACPs as well. So we expect that to continue.

Thank you. Our next question is from the line of Brandon Folks with Canterford Journal. Please receive your questions.

Hi. Thanks for taking my questions, and congratulations on the progress. Maybe firstly for me, just on like Bolvi and the launch of the broader DTC TV campaign, how should we think about the interplay of the broad DTC TV campaign ahead of contracting? And how should we think about the initial effectiveness of it and the interplay between perhaps a broad TV DTC campaign and contracting as the year unfolds?

Yeah, absolutely. So as I said, we're really excited about about the launch of the TV portion of the consumer campaign, which will actually kick off next week. It's a broad campaign, the TV portion. It's meant to be supportive of the earlier launch we did with our digital component. We've been planning for this for a number of years. We've got deep patient insights, HCP insights. We really understand what patients are looking for, and we've tested this with with an enormous amount of actual patients, and it responded very well to them. Market access is in a good position at this point. Medicare, Medicaid, there is a pathway to access. There is a pathway to access for the majority of patients in the commercial space. We're seeing encouraging trends across all three segments, so we have utilization across all three segments. And market access in today's U.S. healthcare environment is broader than just contracting. It's providing a pathway to access. It's providing support services. It's pushing through access. It's also pulling through access. And we're seeing good utilization. As you know, as we've talked, we have a lot of support services available. We're seeing a very high utilization of our PA program. We're seeing a high utilization of our co-pay program. And physicians and HCPs in this space are used to navigating the complexities of market access. They know how to get these products, and all of the products are somewhat treated very similarly. So we think we're in a good spot with where market access is. Patients can get access to the product. Our strategy, as we've been planning for a number of years, as I said earlier, is to drive demand, but also to build awareness. And we've seen through our research that if a patient sees our campaign, they like the campaign, they will ask HCPs about the campaign. And there's a very high likelihood that their request will be granted, so we're excited about that.

Great, thanks very much. And just on a follow-up, just given the news on the SPIN, can you just update us on the latest on the alternative dosing from Embaluc and Alford? Do you expect to make that data public ahead of the SPIN? Thank you.

Hey, Brandon, it's Rich on that. That's happening primarily in a study called Artistry 3, which is looking at less frequent IV dosing regimens. including once every three-week cycle and twice in a three-week cycle. We're accumulating data in those cohorts right now. We will present those data as they mature, and I don't have a specific sense right now of what that looks like over the course of the year, but we can get back to you on that.

And the sub-Q dosing, Rich?

Sub-Q is still underway. I think the team's belief right now is that the less frequent IV will probably be a preferred route versus the sub-Q, but we can't say that definitively. I think for some of these cytokines, and you've seen from the previous data, we've seen original response data with sub-Q presentation. We see pharmacodynamics through sub-Q presentation. The question with sub-Q presentation would be durability of that response, because one of the hallmarks of the IL-2 pathway has been when people respond, you get these nice durable responses. Proleukin originally, same story, it was active sub-Q, but it wasn't as durable. So that's what we're testing in the clinic as well.

Right, thank you very much, and congratulations on all the progress. Thank you.

Our next question comes from Umar Rafat with Evercore ISI. Please receive your question.

Morning, guys. Thanks for taking my question. I have two here, if I may. First, Richard, can you remind us, what's the key clinical readout you guys will get visibility on in your ovarian study for nebulucan, as well as for the melanoma study? the phase three trial, sorry, the phase two trials, and to what extent would those readouts determine whether or not you are absolutely moving forward with the spin, point number one. The second one is, can you speak to the efflux ratio on your orexin molecule and how that compares versus Takeda and what that would mean for the types of doses you guys think are clinically relevant or efficacious doses? Thank you.

More numerous. Recognize that the punchline to your question on the clinical trial is that we're going to spin while both Artistry 6 and Artistry 7 are still underway and blinded. So the key variable for us prior to SPIN is enrollment rate. As we determine where we stand in the overall enrollment, that'll help us measure the amount of time we think we will need before we get to turn those cards over to inform how we capitalize the SPIN. But SPIN should happen in the Q3 timeframe. Enrollment in Artistry 7 and Artistry 6 will be underway. Artistry 7, the ovarian study, is a multi-arm study that has all the appropriate controls that you would expect in a registration enabling study. So it's a very well designed, appropriately controlled study that will lead, that's why we describe it as a registration enabling study. I won't comment on the numerical efflux ratio with respect to the orexin candidates. Obviously, you know, it raises a really important point, though, with respect to these molecules and why I think all of them, each of them, are going to be different. Because it's not just about potency as an orexin 2 receptor agonist. It's about its effective half-life and its effective target engagement. in the human body over time, over the course of a day. So that's what happens as you take the tablet orally, how it gets into the bloodstream, how it crosses the blood-brain barrier, how it gets into the brain, how it reaches target concentrations at the target neurons, and then how long it stays there, or whether it's a substrate for any other types of pumps or other efflux mechanisms. All that stuff has been taken into consideration as we design 2680. But as I always say, none of it matters until you get into the species of interest, which is humans. And now with the Phase I work as well along as it is now, we're excited to actually get into NT1 patients, which is the next step. And all systems are leading into that.

Richard, if I may clarify, I'm thinking back, and maybe I'm not recollecting properly the I recall we had discussed there will be potential interim looks ahead of the spin on the oncology side. Are you saying there's a change in plans? I just want to make sure I understand it the right way, because I thought that was a trigger to move forward with the spin.

We have an ongoing data safety monitoring board with respect to the melanoma study that looks at futility and risk-benefit, and we continue to pass those hurdles.

Got it. Thank you.

You're welcome. I'm looking to Sandy to make sure that's an accurate statement.

Yes, that's right.

Good.

Our next question is from the line of Chris Shibutani with Goldman Sachs. Please proceed with your question.

Thank you very much. Good morning. On 2680, as I think about how we should be interpreting the data that you'll have, Phase 1B proof of concept, across the different subtypes of patients in T1, And I think the expectation is that potentially the potency or dosing level would be different for NT2 and IH. It seems perhaps that you may be emphasizing IH over NT2. And with such a modest denominator, relatively speaking, six or seven or so patients in each subtype, can you help us understand how you're thinking about your positioning of your development plan and whether ultimately next steps may be to pursue specific segments because of the potential differences in dosing required.

Yeah, good morning, Chris. Yeah, that's a really important question because please don't misinterpret any of our comments. They were emphasizing IH over narcolepsy. If anything, it's the other direction, particularly in the wake of the IRA. I think that this orphan indication as a single indication, narcolepsy is really attractive because it's an orphan indication, but it's a larger orphan indication spanning NT1 and NT2. So, if anything, I think that our focus is more likely to cone down into the narcolepsy indications rather than the IH and excessive daytime sleepiness indications, which we will pursue as this biology gets more clearly elaborated with additional compounds. I mean, we're not done here by any stretch of the imagination. In the lab, we see 2680 as the first embodiment focused on narcolepsy given a certain PKPD potency profile. But if this is really central to the sleep-wake axis and that circuitry is more better elaborated, there's other drugs to be developed here. But for the purposes of 2680, the Phase 1B proof-of-concept study is going to focus first on NT1, and that's the core of the bullseye. Then we'll enroll the NT2 patients and the IH patients. You're right. We expect dosing differential based on previous clinical work that's been done by others to between NT1 and NT2, but that's why potency is such an important variable. If you think that you could go as high as several fold higher into NT2 versus NT1, you want to start with as high a potency drug in NT1 as you can get. So far, based on the modeling and the work we've seen at the clinic so far, the data are consistent with our hypothesis going in. Does that make sense?

Great. Yeah, no, that makes sense. And then as a follow-up, a broader strategic question, given all the progress that you're making with separating the companies, Alkermes is domiciled in Ireland, and the revenue and the commercial footprint has always been significantly, if not entirely, in the U.S. As you think about the neuroscience business portfolio, and particularly the potential to expand with 2680, which has certainly vast potential market opportunity, can you talk through the pros and cons and how you and the management team and the board are thinking about ultimately aspiring to be more of a global commercial presence, and if so, how might you do that?

Yeah, it's another good question, Chris. So Alkermes PLC will remain an Irish top coat company with significant operations in the U.S. and in Ireland, but we have a really strong foundation for expansion in the ex-U.S. Interestingly, our psychiatry portfolio, Aristata, Vivitrol, and Evolvi to some extent, really didn't have great opportunities outside the U.S. given the reference pricing in those markets. 2680 is a completely different story. I mean, that's absolutely a global product, and we think about it as such. And so our registration strategy and our teams now are working through the strategy for a global presence. Given the size of the market, on the order of a couple hundred thousand patients in the U.S. and about 3 million worldwide, it's very tractable for a company with our infrastructure to go after an OUS presence with respect to 2680. So we'll give you more information on that as it evolves.

Great. Thanks for the comments.

Our next question is from the line of David Anselm with Piper Sandler. Pleasure to see you with your questions.

Hey, thanks. So just a couple. So on Libalvi, you had talked about potentially a widening gross to net in the second half of this year to the extent that there's new commercial contracting. In the past, you sounded more certain that there will be a wider gross to net or due to the impact of commercial contracting. So is there anything has sort of changed in your discussions with commercial payers that has driven the the revised commentary, somewhat revised commentary, if you will. That's number one. And then secondly, as you think about the cash that's coming in by the Janssen win, can you talk about the extent to which that could be used to seed the oncology business? And just also generally, you mentioned strategic purposes. How are you thinking about use of capital broadly to build out of the neuroscience pipeline. Thank you.

Yeah, I'll start first with the market access. I think the way to think about this, what we've been thinking about this is, you know, the market access profile continues to be established, and it will continue to be established. The most important thing right now is to make sure that patients have a pathway to access across the three channels, Medicare, Medicaid, and commercial, and And we built a solid foundation across all three of those channels. I would say nothing's changed to your question. We are strategically managing growth to net to support our top line growth. And our plan is to continue to determine over time if we need to change our access position within commercial. So we're actively discussing in discussions with all of the commercial payers. regarding the future of Le Balvie. And if we do make a decision that we need to change that profile, our plan is to do so over time. And we'll keep you informed as things progress. But to your question, nothing has changed.

And then on the incoming cash, assuming the final award reflects the interim awards, with respect to the oncology business, it would certainly be helpful in seeding the oncology business. That's not to say we would change the amount that we believe the oncology business needs in order to reach its next data inflection point, which has always been tied to the level of funding that we provide. And then with respect to items beyond that, the cash is obviously a strategic asset, and we could look to potentially augment the pipeline or further leverage the commercial infrastructure with appropriate products at some point into the future, but we'll provide more information as things materialize in that direction.

Thank you.

Thank you. Our next question is from the line of Paul Matisse with Stiefel. Please proceed with your question.

Thanks so much. I appreciate it. I wanted to ask a question on the Baldy and your full year guidance. If you assume that the sequential script growth declines even a little over the next handful of quarters, say, you know, 1% to 2%, even at stable gross to net, you get closer to the low end of your guidance. So I wonder if that's a realistic way to think about this or whether part of the assumption here is that the DTC is going to actually boost demand growth relative to what we just saw sequentially or whether 1Q was maybe just kind of a lighter quarter for various seasonality reasons. Thank you.

Yeah, I'll take that question as well. You know, our guidance has a range of scenarios from, as we discussed earlier, from demand, gross debt, and so forth. We are very encouraged with what we're seeing. Q1, the story for Q1 was a demand story of 16%. We've been at this launch now for approximately 18 months. We continue to see strong uptake and expansion of breadth of utilization. That's probably the best metric that we're watching at this point. We fully believe that building awareness through a direct-to-consumer campaign will also support our demand aspirations over time. Typically what you see with broad campaigns such as this and other categories and also in psychiatry is it usually takes about six to 12 months. to actually see some type of inflection. We think it will be gradual overall, and so we do believe that this is going to support the long-term growth aspirations that we have for the brand, but we're encouraged right now, and we think this is about expanding prescriber breadth, building awareness, and seeing the demand continue to grow quarter over quarter. And I'll just reinforce again, as Ian said earlier, we are reiterating our guidance today, our range, and we're confident in what those ranges are.

Can you say anything about what the top end of your guidance would assume or what would have to happen?

No, at this point, I mean, we provided the outlook. We've looked at a range of possibilities from market access, demand, also with direct-to-consumer. So we're comfortable with where that range is right now. Okay, thanks.

Our next question is from the line of Jessica Fyatt with J.P. Morgan. Please proceed with your questions.

Hey, guys. Good morning. Thanks so much for taking the questions. Just a couple on Lubalzi. Can you remind me of the payer mix between government and commercial in the bipolar market? And can you elaborate on what you mean by a pathway to access in commercial? Where does commercial coverage stand And specifically, I guess, how could the quality of access be improved via contracting? And then I have one follow-up on the erection.

Yeah, absolutely. So, you know, overall, what you see across the category, across all the channels, is typically it's broken into thirds, about a third commercial, a third Medicaid, a third Medicaid. You see a little bit of a change within the bipolar space. There's a little bit more commercial and also a little bit more Medicaid and a little bit less Medicare. So the bipolar market is typically categorized by commercial and Medicare. We think about a pathway to access is broader than just gross to net and doing contracting as well. And that's really the dynamic in the U.S. healthcare system at all. Keep in mind that it's a very large generic market. All of these products, all of the branded products, have to step through generics. So that's not different for what LaVolvi is facing. And providers and HCPs in the U.S. are very comfortable with managing medical exceptions, prior authorizations, and steps through. So our goal right now is to make sure that we're balancing and managing the access profile that would be across commercial, Medicaid, and Medicare, along with the programs that HCPs and patients would need to be able to get access. And we also look very closely, we do a lot of research with patients and also with providers, and we hear really consistently that HCPs perceive that LaVolvi's formulary access is on par with branded competitors. And we see that in terms of the access that's happening within the marketplace at large. Over time, we'll continue to watch what's happening in the commercial space. We watch our NDC block lives. We also have a number of lives that have open access. And so it's not a stagnant market, I can tell you that. It takes a lot of focus and attention, and we put a lot of attention to this as well, too. And so overall, we're going to be managing our growth to net. It's a big strategy for the company, making sure that we have the right access profile to support the long-term growth aspirations of that. And so we're in a good place with that right now. We have a solid foundation.

Okay, thanks for that. And then for the orexin, thanks for the additional color and paired remarks. Should we expect a more detailed update on the SAD and MAD results prior to learning the Phase 1b results later this year?

Jessica, it's Rich. I think that what we're trying to do is move as quickly as we can and being mindful of some of the major scientific meetings that occur in the fall, what the late breaking status would be. So we'll try to present as much data as we can comprehensively in scientific fora rather than just via press release. But I think that the primary goal right now is to finish off the sad, mad, get the Phase 1b data, particularly with respect to the NT1 cohort, as fast as possible so that we get a real sense of the clinical profile of the drug. And then we'll present those data as rapidly and as comprehensively as we can.

Great. Thank you. Our next question is from the line of Yui Er with Mizuho. Please proceed with your question.

Thanks. Good morning, guys. Thanks for taking my question. I know you probably can't say much, but could you sort of just walk us through sort of what needs to, or at least the procedure for the arbitrations in order to sort of get the interim awards finalized? Is there anything else? Should we expect additional interim awards? So that's the first question. I guess my follow-up question is, Can you tell us like how much of the royalties come from TRNSA and Javiera? Thanks.

Good morning, it's Rich. The arbitration procedures has proceeded in a really deliberate and careful way and we have a lot of respect for the way the panel is conducting itself because essentially they're giving the parties the opportunity to brief and make sure that the voices on both sides are heard throughout the process. So the first interim award in January as I mentioned, ticked off the central issue, which is the ability for Janssen to continue to sell the products without paying us a royalty. That was adjudicated in our favor The next question was then, okay, let's start seeing how that applies directly to the various products and the terms of those royalties. And that's what we just learned in the second interim award. The numerical quantification of 2022 and then what 2023 looks like and the fact that each of the three products are being treated independently with different terms. That's check, check. That's now. In the second interim, the panel came back and said the parties have 21 days to alert the panel whether there's any other things we want the panel to opine on. So we're nearing the end of the runway here. I think that this is coning down now to any remaining issues. From Alchemy's perspective, we don't see any outstanding issues. We'll wait to see if J&J has any other outstanding issues, but I think we're approaching the final award.

And then with regard to Trinza and Hafiera, this is based on IQVIA data in the U.S. We would estimate that somewhere between 20% to 25% of volume on a month of therapy basis is related to Trinza and Hafiera.

Okay. Thank you.

Thank you. Our next question is from the line of Jason Gerbery with Bank of America. Please proceed with your question.

Hey, guys. Thanks for taking my questions. Most of my questions have been asked, but I'll ask a couple. Rich, in the past, just thinking about the whole Vivitrol generic threat in whatever shape it takes, you've talked about a lot of the commercial challenges to making or selling a generic of Vivitrol. Given the shift of the business to alcohol, I'm wondering, is this becoming more of a conventional channel product versus when there was more of an opioid component to revenue and starts were occurring in prisons and Addiction clinics, maybe it was a harder product commercially to reach. So just wondering if there's any change that's noteworthy there. And then just as a follow-up, your comment about IRA and the orexins got me thinking. Obviously, two indications, you lose the orphan drug shield. Have you thought about adjudicating two different NCEs in the orexin space, one for narcolepsy and one for IH? Thanks.

Yeah, to the second question, absolutely, yes. I think I was saying earlier, Jason, I think this whole pathway... is so important and fundamental to the sleep-wake cycle, and I think our first embodiment is 2680, but we're already thinking about other ways of engaging that pathway. I wish Vivitrol became more conventional with the advent of the alcohol side. It remains, and I'll let Todd comment. These are definitely different settings of care than your classic medical settings. So it remains incredibly idiosyncratic and incredibly bespoke with still a large overlay of public policy and government intervention in the way that patients get treated.

Yeah, let me just add to that. When we think about Vivitrol right now, 65% of the contribution of the volume is coming from alcohol dependence. We're hitting all-time highs. with utilization for alcohol dependence. At this stage in the life cycle, we're actually hitting all-time highs with prescriber and account breadth as well, and there's a very high receptivity to the storage of Vivitrol for alcohol dependence. It's not a typical retail product, and so we've done a lot of models, looked at analogs as well too, and our expectation is that regardless, if there was a generic injectable naltrexone coming into the marketplace, we don't believe that it would resemble a low-cost, small molecule erosion. And it really comes down to kind of what Rich said as well, too. It's a complex market overall. And the way to think about the complexity of the market is there's various settings of care. It's just not one setting of care that you have to be able to commercialize. There's various payer dynamics. And there's also various fulfillment channels as well, too, which is different. than your typical retail product. So we think it's really complex, actually, the product attributes, but the actual commercialization attributes. So we don't see this as a typical generic erosion.

Thanks, guys.

Thank you. Our next question is from the line of Mark Goodman of SBB Securities. Please receive your questions.

Rich, obviously BD must be pretty important to you, and I know that you're probably out there looking pretty actively for new molecules. Can you just talk about the landscape right now? I mean, do you feel like some of these smaller companies are capitulating on valuations? Are you closer this year than last year on bringing in some new assets from the outside? Thanks.

Hey, Margaret, Rich, yeah, I think that there's – You would have characterized this area as being not very fertile for business development a couple of years ago, and I think it's getting more so. And the cost of capital for small companies is helping. I must say, we have not been... rabid about expanding the pipeline and the R&D spend over the last couple of years being so focused on the launch of Lee-Balvey and getting the erection program and its derivatives and other things in the labs that we haven't discussed moving along. So we're in a nice position where we feel like there's enough in the pipeline to prime the pump to get us going, but we don't feel an urgency to do something. So we're letting things play out. Obviously, the business development team that we have is sophisticated and broad. They're looking at things from late-stage commercial things all the way through to things at ideation that are consistent with our scientific capabilities. But, you know, stay tuned. I mean, we feel like as the neuroscience company spins, it will want to augment its pipeline, but we'll want to do so in a really cost-efficient way.

And erection derivatives, is that referring to the previous question about potentially having multiple erections for the different channels of, you know, with cataplexy, without cataplexy, IH, you know, that kind of thing?

Yeah, and there's a lot to be done as we figure out how to create these small molecule orexin receptor agonists. I think thinking that the full embodiment would be in the first drug is probably naive, so we want to make sure we're ahead of the curve on that.

Okay, thanks Mark. I think we have time for one more question.

That question comes from the line of Douglas Sell with HC Wainwright.

Hi, good morning. Thanks for taking the question. Most of my questions have been asked and answered, but just in terms of the DQC campaign, I'm just curious, do you expect to have a greater impact on the demand for bipolar indication, or do you think it would have more impact on the schizophrenia indication? Thank you.

Yeah, you know, Doug, the way we think about that is it works together. You know, the powerful thing about LaVolvi is that we have a very broad indication, which is not typical for a launch product in the category. And what we've learned over the first 18 months is this is totally an efficacy-driven market, and that's how really LaVolvi is differentiated. So we believe that we have a campaign that is differentiated. We know the media consumption patterns of patients with schizophrenia and bipolar. We know what their habits are. The initial launch of our digital program was really focused specifically on schizophrenia and bipolar. With the TB component of this, the bipolar is a very large market opportunity. There's a lot of switching within the marketplace. Patients switch therapies anywhere between five to seven times over their span, so we know this is a large switch opportunity. So this program overall actually works together. You have the digital component that hits both indications, but then we're really going to activate the bipolar patient through TV.

Okay, great. That's very helpful. Good.

All right. Well, thanks, everyone, for joining us on the call today. Please don't hesitate to reach out if you have any follow-up questions. Thank you.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.