Good morning, everyone. My name is Jessica Fye. I'm a senior biotech analyst at J.P. Morgan, and we're continuing the 42nd Annual Healthcare Conference today with Alkermes. Richard Pops, the company's CEO, is gonna give a presentation on the business, and then we're gonna go into Q&A after that. If you have a question in the room, you can raise your hand, someone will bring you a microphone, or you can submit questions through the portal. But with that, let me pass it over to Richard.
Great. Thank you, Jess, and I'm joined here with, by, Blair Jackson and Iain Brown as well. So good morning, everybody. So I've been looking forward to giving this presentation for a couple of years. This is a new company. Alkermes in 2024 is a profitable, pure-play company in an aspect of the biopharmaceutical industry that is taking on, I think, a renewed level of strategic importance, and that's neuroscience. So we'll talk about that today. I will make forward-looking statements, and one thing you learn in this business is that we do encounter many risks, and we try to articulate them as carefully as we can in our disclosures, like this slide and also in our SEC filings. So we always ask you to take a look at those and consider them carefully.
With that said, here's Alkermes in 2024 in a snapshot with 3 important takeaways. First, this is a substantial commercial enterprise. We have a top line in excess of $1 billion, driven by 4 core commercial products, all developed by Alkermes and all having the potential to continue to grow. This strong and diversified revenue base drives profitability, and it gives us the resources to continue to grow. So second, we have the elements in place to enable that growth. We have proven development capabilities in neuroscience that have developed many products in both neurology and psychiatry through FDA approval into the market. We're leveraging those capabilities to develop and advance new neuroscience candidates that we believe can drive significant value.
Third, because of the extensive work we've done over the past several years to drive operational efficiency, we're positioned for sustained profitability and significant cash generation. So that's a rare set of attributes, and so we enter 2024 in a strong position. The simplicity and the power of this position was enabled by an eventful 2023, which repositioned the company and established this strong foundation for growth. We had an ambitious agenda last year, and we successfully achieved all the major goals we had set for ourselves. So taking it from the top, we entered 2023 in arbitration with J&J and prevailed in that case decisively, which reinstated significant cash flows due to us and strengthened our balance sheet and enabled us to raise our financial expectations during the year.
We had another pending legal proceeding related to Vivitrol and its patent estate, which we also resolved favorably with a settlement that clarified Vivitrol's patent exclusivity for several years. We entered the year with an ambitious goal of generating critical decision-making data for our orexin-2 receptor agonist, ALKS 2680, in a multifaceted phase Ia/phase Ib program. We were successful in doing that, generating narcolepsy Type 1 data that support advancing it to phase II this year. We completed the separation of our oncology business, a major milestone for the company, freeing resources and focusing our R&D efforts in neuroscience. We delivered a significant element of our multi-year program to drive operational efficiencies by announcing divestiture of our Athlone, Ireland, GMP manufacturing facility at the end of the year.
We met our goal of continuing to drive our top-line revenue from proprietary products, including the continued strong launch of Lybalvi. The accomplishments of 2023 simplified the business and set up the four focused strategic priorities for 2024. First is to continue to drive strong commercial growth and profitability. With growth from our core commercial products, coupled with efficiencies from our streamlined operating structure, we believe the business is positioned to drive strong profitability in 2024. Second is to advance the 2680 orexin program as aggressively as possible. Based on the data we've already generated in Narcolepsy Type 1, we're moving rapidly to initiate phase II, and as we generate phase 1b data in Narcolepsy Type 2, we expect to move forward in that indication as well. Third is to continue to expand the neuroscience pipeline.
We expect to advance candidates emerging from our own labs, as well as evaluate external pipeline opportunities, leveraging our scientific, development, and commercial expertise in neuroscience. And fourth is to plan for significant cash generation. The expectation of profitability and cash generation drives an increased focus on capital allocation and potential opportunities to both build the business and return capital to shareholders. This is the revenue picture over the past four years. You can see that it's characterized by growth and diversification. So today, Vivitrol, Aristada, Lybalvi, and Vumerity all contribute to a billion-dollar top line. Our newest and fastest-growing product... Did I click? Yes. Our newest and our fastest-growing product is Lybalvi, for the treatment of schizophrenia and bipolar I disorder. Lybalvi is a once-daily oral atypical antipsychotic composed of olanzapine, which is an established antipsychotic agent, and samidorphan, a new chemical entity that we invented.
Its place in the market is based on efficacy. Efficacy established by the long clinical track record of olanzapine and our Lybalvi clinical program. In a market that's characterized by millions of patients and frequent treatment switches, Lybalvi represents an important new treatment option for healthcare providers. The success of Lybalvi's launch is best represented by the data. On the left is a chart of total weekly prescriptions since launch, by week, and then smoothed with a four-week rolling average. And then on the right are quarterly reported net sales. So you see strong, consistent growth, and we expect that growth to continue. Lybalvi entered the market with data from phase III clinical trials, FDA approval, and a label. That's just the beginning.
In a market as competitive as the atypical antipsychotic market, new medicines need to establish their place in the treatment paradigm through real, real-world use and experience. We have continued to build the clinical evidence base for Lybalvi. Last week, we announced data from a long-term phase III open-label extension study that showed that patients with schizophrenia or bipolar I disorder who continued taking Lybalvi demonstrated stability in their symptoms, minimal changes in their body weight, lipid, and glycemic parameters for up to four years, and a safety profile consistent with what we had seen in previous studies. Lybalvi's potential as a foundational treatment that patients can start on and stay on is exemplified by these data, the potential for long-term symptom control and stable weight, lipid, and glycemic profile.
That was our focus from the outset: to make a medicine that could be used over the long term by patients suffering from a serious chronic illness of schizophrenia or bipolar I disorder. This is also true of Aristada, our long-acting injectable for schizophrenia. Like Lybalvi, Aristada is based on a novel molecular entity and designed to address the real-world needs of patients and providers. In this case, the need is for a flexible, long-duration dosing regimen of a proven antipsychotic. Aristada's annual net sales are shown on the right. It has delivered sixty... consistent growth, and we will believe it will be continued to be an important contributor to our revenue mix for many years to come. The third proprietary product we commercialize is Vivitrol. Vivitrol is a long-acting injectable for the treatment of alcohol dependence and opioid dependence.
It's an extended-release version of an opiate antagonist, providing therapeutic levels of naltrexone for a one-month period. Alkermes pioneered the use of injectable antagonists in these indications, and we're the leader in these complex treatment paradigms and market environment. Vivitrol's growth over the last several years has been driven primarily by the alcohol dependence indication, and we believe we're well-positioned to further drive further uptake of Vivitrol in that developing market. And then finally, Vumerity, which is a medicine discovered and developed by Alkermes that we licensed to Biogen for commercialization. Vumerity is a novel oral fumarate for the treatment of relapsing forms of multiple sclerosis. We receive a 15% net royalty on worldwide net sales, and you can see the revenues in the graph on the right.
VUMERITY is an important treatment option in the MS market, and it offers significant long-term revenue growth opportunity and cash flows for Alkermes. So these four products, LYBALVI, ARISTADA, VIVITROL, and VUMERITY, comprise the critical elements of our commercial revenue. So let's move to what's coming next, deriving from our proven drug development capabilities and our most advanced pipeline asset. Let me back up one. First, just to level set, Alkermes has deep experience in developing FDA-approved neuroscience medicines. VIVITROL is based on biocompatible polymers. ARISTADA is a new molecular entity that enables long-acting activity. LYBALVI is a new molecular entity that confers new pharmaceutical properties. VUMERITY, another new molecular entity, all developed by our scientists. These medicines result from capabilities built over many years in the labs, in molecular design and medicinal chemistry, and then in the clinic and in front of regulators.
There's no substitute for experience in drug development. This experience is being brought to bear now in our orexin program for narcolepsy. Orexin dysfunction is a well-defined opportunity for new drug development. In narcolepsy, low orexin levels result in excessive sleepiness and poor regulation of REM sleep. Narcolepsy is an orphan disease, but a substantial one, affecting approximately 200,000 people in the U.S. and 3 million people around the world. 70% of people with narcolepsy have narcolepsy Type 1, we call NT1, which is distinguished by cataplexy, which is sudden muscle weakness triggered by strong emotions, and low or no orexin levels in the brain. People with narcolepsy Type 2, or NT2, experience daytime sleepiness but not cataplexy and generally have normal levels of orexin.
Genetic and pharmacologic evidence suggest that orexin receptor agonist, particularly orexin-2 receptor agonists, could be useful for mechanistic treatment of narcolepsy. If the biology is clear, the chemistry is not. Making an orexin-2 receptor agonist is a complex molecular design challenge requiring optimization along several axes, some of which are shown here. This radar plot visualizes a compound's attributes along these axes, higher, higher scores radiating outward, meaning better performance. The goal is to make a balanced molecule that scores well across all of these parameters, yielding one that is highly potent, highly selective for the orexin-2 receptor, orally bioavailable, that can cross the blood-brain barrier into the brain, and engage the receptor over a time course consistent with the sleep-wake cycle. Different molecules have different properties, and it's challenging to optimize along all these axes.
For example, a compound could have excellent potency and selectivity, but not access the CNS in concentrations sufficient to drive efficacy at acceptable doses. Alternatively, a molecule that has good properties but a short half-life would have to be dosed multiple times per day. And less potent molecules or selective compounds could have undesirable off-target effects. This is precisely why the various molecules that we've seen enter the clinic have had divergent results. They're all quite different. And this is where our experience comes to play. From the outset, we stipulated that potency and selectivity are essential but insufficient. We have deep experience in small molecule drug design, and our origins are in optimizing PK/PD relationships. So we've been evolving the chemistry deliberately to optimize multiple parameters. This is what we set out to achieve with ALKS 2680.
It's designed with a specific therapeutic goal in mind: improved wakefulness, duration, and quality, a PK/PD profile that mirrors the natural sleep-wake cycle, cataplexy control, a low therapeutic dose with once-daily oral dosing, an acceptable safety profile with a wide therapeutic window. ALKS 2680 is our first candidate to emerge from that chemistry effort, and it's advancing quickly in development. It is, by necessity, a highly potent, selective orexin-2 receptor agonist, greater than tenfold more potent than orexin-A and greater 5, than 5,000-fold more selective for the orexin-2 receptor compared to the orexin-1 receptor. But it's more than that. The initial phase I data showed the pharmaceutical properties that we desired. It's orally bioavailable with a PK profile that supports once-daily dosing, mimicking the natural sleep-wake cycle with a half-life of 8-10 hours.
We covered a lot of ground in our clinical program last year. We generated single and multiple ascending dose data in healthy volunteers and recently completed our phase 1b cohort of the NT-1 patients, yielding a go for phase 2 in that indication. NT-2 and idiopathic hypersomnia patients are being enrolled in the phase 1b now, with data from those cohorts expected in the next few months. A major goal for 2023 was to complete the first evaluable cohort of the first four NT-1 patients in time for presentation at the biannual World Sleep Meeting, which was held last year in Brazil.
Our data were presented there, which gave our team a chance to interact with many of the major global thought leaders in narcolepsy, as well as patient advocacy organizations, to gather feedback on the data and gain input on the design of the phase II program. We've now completed the full NT-1 cohort, totaling 10 patients, and have a data set supporting our rapid advancement into phase II. From an efficacy standpoint, we saw statistically significant and clinically meaningful improvement of maintenance of wakefulness scores at each dose level, 1, 3, and 8 milligrams, with a dose-dependent magnitude and durability of effect. This enabled us to select our dose range for phase II in NT-1, which we believe can accommodate expected and observed patient heterogeneity. So we plan to evaluate 4 milligrams, 6 milligrams, and 8 milligrams administered once daily in the morning in the phase II NT-1 study.
Safety and tolerability are just as important as efficacy, and here we saw encouraging data as well. 2680 was generally well-tolerated at all doses tested. Treatment-emergent adverse events were transient and self-resolving and mild in severity, with the exception of one moderate case of nausea, which resolved with food intake. No serious AEs or AEs leading to discontinuation. The AEs were generally consistent with the initial four NT-1 subjects. The new drug-related treatment-emergent AEs seen in the full cohort included nausea, decreased appetite, and elevated heart rate, with no occurrences of visual disturbances and no occurrences of treatment-emergent liver enzyme elevation. With the completion of this cohort, we have the confidence and information we need to launch phase II. We are still enrolling NT-2 and IH patients in the Ib.
As those data are generated, our goal is to select doses and proceed to phase II there as well. So this is what the design currently of the planned phase II program in narcolepsy Type 1 looks like. This is a parallel design, four-arm study, randomizing NT-1 patients to either 4, 6, or 8 milligrams of ALKS 2680 or placebo, administered once daily for 6 weeks, followed by an open-label extension and a safety follow-up. The primary efficacy analysis will be conducted at the conclusion of the six-week double-blind phase. We expect the phase II design for NT-2 will look very similar, but with different doses. We currently plan to enroll both NT-2 and IH patients, given the similarity of patient populations, which would enable us to expand the safety database to support registration.
The NT-1 phase II study is designed to capture standard endpoints familiar to regulators and clinicians, as well as exploratory measures designed to provide additional information regarding patients' experience with this new approach to treating narcolepsy. The planned primary and secondary measures will include quantitative Maintenance of Wakefulness Test, the Epworth Sleepiness Scale, and cataplexy rates. In addition, we plan to be exploring certain patient-reported outcome measurements in assessing sleep architecture. The study will be conducted at multiple sites around the world, and we're moving quickly to initiate it as fast as we can. We're excited about this program, while cognizant of the risks and failures of other programs and the difficulties of establishing new mechanisms in CNS disorders. As a focused neuroscience company with the capabilities we've just described, we expect the pipeline to grow.
We gravitate toward development programs within the framework described on the left, where there's strong biological rationale, challenging molecular design, a clear clinical pathway with early proof-of-concept potential, alignment with our expertise, and importantly, in this intense payer environment, the potential to significantly advance the standard of care for patients. We expect the orexin pathway to open additional pipeline opportunities for us, and we're currently pursuing those in our labs. Our historic strengths in psychiatry and neurology, and we plan to build in those areas by advancing internally developed neuroscience programs and exploring externally sourced pipeline opportunities. The goal is to build a balanced pipeline of candidates with promising medical and market opportunities, but with independent and uncorrelated risks. We'll finish by showing how all of this positions Alkermes for sustained profitability and significant cash generation.
The combination of our commercial performance and our efficient cost structure is expected to drive meaningful profitability. We'll provide our full financial expectations for 2024 in February on our earnings call. But at a high level, we expect revenues from our proprietary products, VIVITROL, ARISTADA, and LYBALVI, to continue to grow and deliver more than $1 billion of sales in 2024. These proprietary products will be supplemented by our royalty and manufacturing revenues. For modeling purposes, I'll note that the royalty stream related to the U.S. sales of Invega Sustenna will expire in August of this year, 2024. On operating expenses, we've worked hard to calibrate our operating structure to support the needs of the business going forward. The most significant change compared to 2023 will be in R&D.
Following the separation of the oncology business in November of last year, expenses have been significantly reduced, with approximately $150 million of oncology spend removed from the R&D line in 2024. So together, we expect our top-line performance and sharp focus on operating efficiencies to drive approximately 30% EBITDA margin in 2024. We enter the year well-positioned financially, with a strong balance sheet and a clear outlook for the various elements of our business, and we're quite excited about the future for the company. So I'll end with another quick look at the 2024 strategic priorities, which are straightforward and derive from the increased simplicity and focus of the business: deliver strong growth commercially and profitability, advance 2680 into phase II, expand the pipeline, and prepare to move into a phase of significant cash generation.
With that, I'll finish, and we'll open it up for the questions. Thank you.
Great. Thanks for the presentation. I guess I wanna start on the bottom of this slide, where you mentioned the plan for significant cash generation and an increased focus on capital allocation. I think you talked about expanding Alkermes' own capabilities, but also potentially returning cash to shareholders. What form could that take, and I guess over what time horizon are we contemplating here?
It's something we're actively focused on now at the board level because as we look at the long-range plan now, with the more streamlined business and the top line continuing to grow, we will generate significant amounts of cash. So we have a number of different places we wanna allocate capital. Obviously, top of the list is to identify sources of a return for shareholders: LYBALVI launch, ALKS 2680 program, and making sure those get all the resources they need. We want to expand the pipeline in a way that's measured, consistent with our profitability goals.
But at the same time, we feel like we should be able to do that and, given where we think the valuation is relative to our intrinsic value, operate it in a way where we can actually return capital to shareholders, and the preferred way would be probably through share repurchases. And I think that you'll hear more about that as we go through the year and as we deliberate this at the board level.
Great. And, expanding the pipeline in a measured way, what's the kind of... I don't know if there's an ideal mix between kind of internal and external expansion, and if we think about business development, maybe you can just touch on, you know, what Alkermes is interested in from a biz dev standpoint.
I think when we look at the new company in 2024, we've checked so many boxes that we wanted to check in terms of the profile of the company, with its substantial top line, its profitability, exciting pipeline asset. The one box that we need to check more aggressively is the breadth of the pipeline. The best way to expand your pipeline is through your own internal candidates. You know all of their strengths and weaknesses, you know the IP, you know everything about them. The second-best way is through acquiring assets that you have a deep understanding of the biology or the chemistry of both, or the clinical or the regulatory setup. We think that there is a chance to do both.
Our pipeline internally derives largely from what we've been doing in the sleep-wake cycle with the orexin program, and that's yielding additional candidates that we're evaluating preclinically this year. But we're also now, with this very clear R&D focus, there are things within our lane on the outside that we're evaluating. And there's been fairly high cost of capital for small cap companies for the last couple of years. There are opportunities out there to look to expand the pipeline, but we don't plan on doing anything, you know, heroically gigantic that's gonna change our R&D spend, so we don't hit the profitability measures that we're dedicated to meeting from a management perspective.
Got it. When you talk about interrogating the sleep-wake cycle and yielding additional candidates, is that additional orexins, or is that sort of outside of orexins?
Both. That circuitry in the brain, what's called the Orexin/hypocretin pathway, it is the central controller of alertness and wakefulness for humans. So narcolepsy is almost the most purified embodiment of that, 'cause you're missing that neuropeptide, so you're sleepy all the time. But you can think about other clinical indications where fatigue is a part of the presentation of the disease. So if you could address that symptom alone, rather than disease modification for the overall diagnosis, but for that particular symptom, it could be very constructive in the treating of those patients. So we're looking at a number of things preclinically, whereas the chemistry space is quite restrictive. It's very hard to make these potent orexin agonists that cross the blood-brain barrier, but we have a suite of those.
Now, we're interrogating the biology. Where else can we use it, where we think clinically it's a clear path to registration and indication outside of narcolepsy?
Got it. The updated narcolepsy Type 1 data you just provided, when should we expect to see kind of a more detailed, either a kind of conference presentation or publication, where we could see more, like, efficacy details?
The efficacy details are actually sort of dog bites man. The profile of this drug is this dose-dependent increase in wakefulness in the MWT test in patients with NT1. It's really quite exciting because we with increased doses between 1, 3, and 8, you see increased wakefulness and increased duration of wakefulness. We'll present those data in whole, either at the Summer Sleep Conference or the Fall Sleep Conference. One's in Europe, one's in the US, just depends on how we aggregate the data for the abstract submission dates. But the principal takeaways are the ones we've talked about here.
We know the dosing for phase II, and what we wanna now demonstrate in phase II is what the profile looks like with continuous, repeated dosing over a six-week period, rather than just in a one-dose, four-way crossover study. That's the next, that's the next hurdle for us.
Got it. And then maybe switching to NT2 and IH. I think you talked about potentially a similar next step trial design for NT2 as you're looking at in NT1. And I thought you said something about enrolling more IH patients for safety. Is that in the same study?
Yeah.
Is that a separate study? How does that work?
So in the diagnosis, NT2 and IH, almost interchangeable diagnoses often, and so the patients present fairly similarly. They have orexin levels in their brain, but they respond to orexin agonists, what we've seen in previous studies. So the hypothesis is that you need a higher dose. So what we're testing in a blind fashion now, but we've increased the dose from the NT1 dose by 2-3x. We'll enroll those patients, and we'll see how they respond. In the phase II, we'll enroll both NT2 and IH patients and just continue to build the exposure and safety database. For phase III, we'll probably focus on the narcolepsy indication alone of NT1 plus NT2.
So in an ideal scenario, if you're starting phase II in NT1 this year, when should we think about seeing the results of that trial?
Let's get it started first. I think for just dead reckoning, you'd say that it'd probably take about a year to enroll a study like this. The design I showed you with group sizes of 15, 4 times 15, 60 patients, it's gonna. It's a global study. There'll be multiple sites around the world, so site activation will actually be the most rate-limiting component of our determining the time. So we'll give more guidance as we get. The protocols are being finished now. We're going to you know, CROs and IRBs and doing all that legwork now. We'll probably have a better sense of that as we move into later in the quarter.
If we fast-forward and think kind of commercially, can you just talk a little bit about where you see orexins fitting into the treatment paradigm in narcolepsy?
You know what? I'm gonna give Blair a chance to speak because you've been tired of me and—
All right.
Go ahead.
No, I think, I think this is a space that, as you know, has evolved a lot over the last, you know, 5-7 years, and obviously with the oxybates that were introduced into the marketplace, it provided finally for these patients an option for treatment. But when we talk to these patients, what we find is they're still deeply dissatisfied with what's available to them. They don't tend to feel very good in the day. There's disruption in their sleep in the evening. So something like the orexin mechanism can fundamentally change this marketplace and make these patients more functional over the course of the day. So we see this being very much a first-line treatment.
I think it remains to be seen longer term, how other treatments adjunctively would interact with that, whether that be the oxybates or some of the other drugs, the histamine modulators that are out there. But we very much see this as a first-line treatment within the marketplace, both in NT1 and NT2.
What's interesting is that narcolepsy, particularly Narcolepsy Type 1, is an absence of this neuropeptide. So conceptually, the idea is: Can you make a small molecule to replace the functioning of a natural neuropeptide?... and can you do so with a waveform, a pharmacokinetic profile that's consistent with the sleep-wake cycle? If you do that, you should go a long way to ameliorating the symptoms of the disease. And I think that's the promise of the early clinical data that needs to be borne out in longer studies. But I think there's a real chance for a transformational approach to treating the disease.
Maybe coming back to some of the 2024 financial projections you put out there, including the, I think, 30% EBITDA margin. Should we think of that as a sustainable margin? Is it possible to kind of expand from there? I'm trying to think about the balance between, like, kind of continued top-line growth, but maybe also more R&D investment as orexin in the pipeline kind of moves forward.
Well, as the business simplifies now, it's a really nice opportunity to articulate what the priorities are of the company. We are gonna be a profitable company from the get-go now. I mean, we're, as long as our revenues are in place and we can manage our cost structure, we'll be a profitable company going forward. We put out our goals for 2024 in terms of our EBITDA margin. You'll notice we're gonna move away from the parlance of include J&J revenues, don't include J&J revenues, 'cause in 2024, the U.S. settlements come off anyway. The business is quite clean. So when we guide from this point forward, we'll guide to our...
As we typically our revenue, our profitability expectations, and each year we'll make a determination about the best capital allocation, but with this commitment to ongoing profitability.
So maybe kinda coming back around to one of those growth drivers, LYBALVI, can we spend a little time on your strategy to kind of continue driving the breadth and depth of prescribing? You know, whether it's the number of prescribers who have written the product or who you wanna see writing it, and kind of where that could go.
It's nice now because at the beginning of the LYBALVI launch, there's all these unknowns, like, how does your drug actually fare in the real world? You have clinical data, and in our case, it was clinical data that was hinging on this idea of there being a differential weight profile, and was that gonna be observed in the real world? And two years into it now, I feel like that's settled business. People know that LYBALVI is a differentiated product from, from olanzapine. And the data that I referred to and that we put out last week is four years of follow-up, really interrogating that. Patients who stay on this drug, does their weight stay stable? Do their metabolic parameters stay stable? Do their glycemic index...
All that stuff looks really, really favorable to us, which is a long introduction to saying our job now is execution. This is a very big market. There's a lot of players. There's a lot of churn. 60,000 switches each month occur, and so the way you get in that flow to pick up new patients is through personal promotion, share of voice, DTC advertising to keep awareness high, and just a continuous execution across that. So I think that chart that I showed of the growth, it's almost this linear growth since launch, and we expect that to continue.
So is the growth we've seen so far benefiting from the DTC campaign that you started last year? I think you talked about kind of it taking time to kick in.
Yeah.
So is there still more to come?
Yeah, I think it's beginning to be feathered into those results that you see now. And so we started in 2023. We had a pulse in the spring. We went fairly quiet in the summertime, then pulsed again in the fall. This year, I think we'll probably be more continuous in the first half of the year. You learn as you go, but I think, as I said, it's just part of the ongoing mix of how you keep the name of the brand, the awareness of the brand, and its relevance in front of patients and providers.
What do you estimate the mix is between schizophrenia and bipolar?
It's about 50/50 now. Yeah.
Does that change? Is it dynamic or...
It's been fairly stable. The DTC broadcast that you see on television, that's focused on bipolar, so we see a real opportunity for growth in bipolar. But you've seen just in the last few weeks, a lot of focus on schizophrenia, and schizophrenia is really a place where LYBALVI has a great foundation because of that monotherapy efficacy of Olanzapine that's so well-credentialed. So we will stay focused in schizophrenia as well.
Maybe on the reimbursement side, where are you, or what's the current formulary positioning, and are you in talks to improve that positioning at all? And kind of related to that, how should we think about gross-to-net this year relative to last year?
I'll start, and then I'll let Iain chime in here. There are three lanes of business, particularly as you look at schizophrenia and bipolar. There's government pay, which is Medicare, Medicaid, and then there's commercial. Right now, for Lybalvi, the bulk of the business, over 75%, is in the government channels, where our access is almost statutorily mandated. In all, I should just be clear, for all these drugs, when you say your access is open access, it means failing multiple generics and doing some type of prior authorization or medical exception to get on a branded medication. That's table stakes. We know how to work through that. Commercial is where the question mark is because commercial, you start without any commercial contracting. They tend to want significant rebates to put the drug on the formulary.
But even if the drug is not on the formulary explicitly, there's still a path to access through most commercial channels, and that's what we've been working through for the past two years. So we've not contracted aggressively in commercial. Our gross to nets are favorable for that reason. But as this goes from being zero to almost $100 million in the second year, circling $200 million in the third year, the pressure builds. The payers would like more, like to have a rebate because they see this flowing through their channel, and we would like to get more access and not be restricted as the business builds. So our expectation is that we didn't contract aggressively or much at all in 2023.
Looking into the first half of 2024, we don't see that changing much, but the back half, we could see expanding our contracting as the brand continues to grow. I know, Iain, if you wanna elaborate on that?
I don't think there's much more to add there.
Okay.
I think, you know, the gross to nets have been relatively consistent for the last 18 months of 26%-27%. As we enter 2024, I think we're in a similar position as we were as we entered 2023. We said we think the next 6 months are gonna be relatively consistent again, but then they could widen, depending on the contracting strategy in the second half.
I think we're about out of time, so we'll stop there. Thank you.
Thank you, Jessica.