Alkermes plc (ALKS) Earnings Call Transcript & Summary

Good morning, everyone, from the Virtual JPMorgan Healthcare Conference. My name is Cory Kasimov, and it's my pleasure to introduce our next company, Alkermes, and Chairman and CEO, Richard Pops. Please note that following this presentation, we will have a Q&A session where you have the ability to submit questions via the conference portal. So with that, Rich, thanks for being here, and let me turn things over to you.

Thank you, Cory. Good morning, and good to see you. And hello to everybody on the virtual presentation. So this year's strategy, and therefore, this presentation, is focused on revealing and elaborating the value that's headed in this distinctive company. In 2020, we demonstrated the resiliency of our people and our business, and we added new scientific, financial and governance elements to the story. So 2021 is about focusing on translating all of this into a growing valuation. So on the next slide, I will be making forward-looking statements. And as always, in these presentations, I encourage you to look at the risk factors described in our quarterly and our annual filings. So on the next slide, let's start at the top. Alkermes is a special company, with a distinctive mission and a disproportionate impact in the community. We advance cutting-edge science to make innovative medicines that map onto the real-world issues facing patients suffering from some of the most important health issues of our time. But it doesn't stop with the medicines. We are a fierce and effective advocate for a systemic change at both federal and state levels to help improve treatment systems for patients with serious mental illness and addiction. We are very proud of what we do and the impact that we have. It's measured each year in hundreds of thousands of lives, patients, their families and their communities. Moving to Slide 4. In a challenging 2020, we identified our key strategic priorities and held ourselves accountable to execute against them. Job 1 was commercial execution for VIVITROL and ARISTADA to protect our commercial business and adapt to an environment that changed dramatically in March. As COVID emerged, and access to physicians and treatment centers became restricted, we adapted our approach to maintain continuity with prescribers and caregivers. We developed a hybrid promotional model tailored to each territory, combining in person and digital interactions. This model will endure. It became the basis for launch planning for ALKS 3831, which is our new oral antipsychotic candidate, which we expect to be the next important product in our psychiatry portfolio and a new long-term revenue stream for the company, once it is approved. VUMERITY, a medicine we developed for the treatment of MS, represents another long-term revenue opportunity. Commercial responsibility for VUMERITY lies with Biogen, where it took on more significance during the last year, and recent trends for its performance are encouraging. The second priority was to advance our highest potential R&D programs in the face of a range of unexpected obstacles from limitations on access to our own laboratories to the closure of certain clinical trial sites around the world due to COVID-19. During the year, we prepared for and completed a successful advisory committee meeting for ALKS 3831, which affirmed the clinical meaningfulness of the data generated in the pivotal program. We significantly advanced 4230, now called nemvaleukin, and hit key milestones despite the pandemic. And I believe we were able to build momentum during this operationally challenging year because of the emerging efficacy signals being seen by investigators at sites around the world. And we entered 2021 positioned to continue this momentum. And we met our goal of nominating our first clinical candidate from our HDAC inhibitor program, an exciting area of neurobiology that we'll discuss a bit later. Finally, the third priority is focused on the efficient management of the business from a financial and operational perspective. As the pandemic evolved, we modeled a range of potential revenue disruptions and made adaptations to our cost base throughout the year. In December, we announced a very specific value enhancement plan designed to drive growth, improve financial and operational performance and enhance shareholder value. The plan includes a commitment to multiyear profitability targets, a focus on the company's cost structure, potential strategic opportunities and continued governance enhancements. We think it provides a solid foundation for future valuation growth. Turning to Slide 5. For 2021, we are similarly focused in 3 major areas. First, to continue to grow and diversify our commercial revenues. We have a substantial and growing top line, driven by important medicines conferring real-based benefits to the large numbers of patients. From an economic as well as a medical perspective, we want these numbers to grow. VIVITROL, ARISTADA, VUMERITY and ALKS 3831, once approved, this is a valuable portfolio, each a distinctive medicine with its own value proposition. Second is to demonstrate the value of the R&D investments that we've been making. After being relatively quiet in 2020, in 2021, you'll see us reveal more of what we've been doing in our focus areas of neuroscience and oncology. At the top of the list is nemvaleukin, which is now moving more clearly toward a registration pathway based on the building efficacy information in the program. We will engage in a partnering process for nemvaleukin this year, particularly as we build the evidence supporting the anti-tumor activity of the subcu regimen. You'll be hearing more about ALKS 1140, the first selective HDAC inhibitor from our platform, with potentially using a range of neurological disorders. We formally nominated 1140 in December and plan to begin first-in-human studies this year. Nemvaleukin and 1140 derived from scientific platforms and capabilities we've been building for several years. Later this quarter, we'll host an Investor Day to give you a better understanding of these programs and some insights into additional candidates that we expect to emerge. The third area of focus is on profitability, making good on the commitments we're making in the context of our value enhancement plan. It's important to note here that achieving our targets is not based on unrealistic expectations of revenue growth. It's based on effective cost management across a range of revenue assumptions: commercial, R&D, cost management, these are 3 powerful levers. Next slide. The platform, the foundation for our revenue growth is our distinctive commercial infrastructure. We compete in highly complex and dynamic environment, much different than many other biotech companies. As a result of the pandemic, telepsychiatry use is widespread, and we expect it will continue, as will patients' restricted ability to interact with health care providers. The dominant payers in our markets are government, federal and state, through Medicare and Medicaid, payers that restrict access to new medicines and are highly focused on value. We have adapted to navigate this environment. We have a strong platform for commercializing VIVITROL and ARISTADA and for launching 3831, once approved. Next slide. So with that as an introduction, let's turn to our commercial franchises, beginning with addiction and VIVITROL. On the next slide, you'll see VIVITROL is a singular product, addressing a major public health need in addiction. It's an extended-release opioid antagonist administered once monthly by injection. It's indicated for the treatment of opioid and alcohol dependence, and both indications are relevant to its future. Turning to Slide 9. For those of you who have been following this story, you know that COVID had a major impact on access to addiction treatment last year. The encouraging news is that access to treatment has improved as we exit 2020. On the left is a plot of VIVITROL net sales, including the trailing 12 months ending Q3 2020. On the right is the 4-week moving average of VIVITROL units through Q3. You can see a sharpened significant drop in the green line in the March-April time frame, followed by recovery driven by the adaptations we made and a gradual reopening of treatment centers across the country. On to Slide 10. For 2021, we have some new elements to the plan. Opioid addiction continues to be a major public health issue and focus for us. Government numbers for 2019 report 1.6 million patients with opioid use disorder, with many of them receiving medication, although some advocates believe these treatment numbers are overestimated. Alcohol dependence has been a growing part of VIVITROL use, and we intend to increase our focus here in '21. There are many patients, an estimated 14.5 million in 2019. And while the use of medication for the treatment of alcohol dependence is still limited, it has been increasingly accepted in the treatment paradigm. Our focus in '21 will be on increasing awareness of VIVITROL as a treatment option among providers, caregivers and patients and thereby driving adoption. Interestingly, we are also aware of new research related to VIVITROL and methamphetamine use, which has reemerged in many areas of the country as a significant public health concern, if not the primary addiction issue in the community. We are looking forward to the publication of data from a large NIDA-sponsored study, investigating VIVITROL in combination with bupropion in patients with moderate to severe meth use. In contrast to opioid and alcohol dependence, there are no approved treatments for methamphetamine. We believe these data will initiate an important dialogue around this growing public health issue. Next slide. Now psychiatry, anchored by ARISTADA and poised for growth. Turning to Slide 12. ARISTADA is a long-acting injectable medicine, particularly well suited for today's environment, an environment characterized by a serious focus on economic value and one in which access to health care providers is limited. ARISTADA is a new molecular entity designed by Alkermes scientists specifically as a long-acting injectable with a favorable pharmacokinetic profile and product presentation. On the next slide you see ARISTADA is the fastest-growing LAI in the market. On the left side of Slide 13, you see ARISTADA net sales, including the trailing 12 months ending Q3 last year. On the right is a plot of the prescription growth rate, ARISTADA versus the aLAI market. Year-on-year growth of 18% versus 5% for the competition and maintaining growth quarter-over-quarter in the midst of the pandemic, which is remarkable given all of the disruptions. These results speak to the uniqueness of the ARISTADA product offering. So moving to Slide 14. You'll see that ARISTADA is the only long-acting treatment for schizophrenia that provides single-day initiation with the INITIO regimen and the option for dosing only 6x a year with our 2-month 1064 dose, a low barrier to initiation in the hospital or in other acute settings, combined with the need for only 6 injections a year to maintain therapeutic levels of effective and well-tolerated antipsychotic. This is what we mean by developing medicines that map onto the real-world needs of patients suffering with chronic disease. On Slide 15, from a market opportunity perspective, the antipsychotic space is attractive. LAIs are the largest branded segment with about 2 million prescriptions written each year. Although they're not the most commonly used agents, we believe there's plenty of growth opportunity ahead for aLAIs and for ARISTADA. The most commonly used agents are the orals, with approximately 15 million prescriptions annually just for schizophrenia. This is largely a generic market but one where branded agents can still be successful due to the serious unmet needs that were made. Oral antipsychotics are often commonly used in bipolar disease, which is a different market with a different payer profile. The distinction between schizophrenia and bipolar and the use of olanzapine in both underscores the opportunity for ALKS 3831 and the potential to expand and leverage our presence in the psychiatry market. So let's turn to that now in the next slide. Following potential approval, ALKS 3831 will be launched as LYBALVI. LYBALVI is a daily oral antipsychotic designed to offer the efficacy of olanzapine, while mitigating its primary clinical limitation, which is the potential for excessive weight gain. We achieved this by the addition of samidorphan, a new molecular entity developed by Alkermes. It comes as a fixed-dose combination in a bilayer tablet of samidorphan and olanzapine in various strengths. Our NDA resubmission is under review with FDA with the PDUFA date of June 1, 2021. Turning to the next slide. Our market research underscores the perceptions around olanzapine and unmet needs in the market. And therefore, the opportunity presented by LYBALVI. On the left, you can see that the majority of surveyed health care providers agree that olanzapine is one of the most efficacious oral antipsychotics for schizophrenia and bipolar I, 71% and 50%, respectively, in this assessment. At the same time, the right-hand figure shows that weight gain is a major concern for these patients. The box on the lower right provides a critical insight into this market. And that is the extent of the churn. Schizophrenia and bipolar disorder patients commonly cycle through 5 to 7 treatment options on average. And they're on the order of 70,000 treatment switches every month. This reflects persistent unmet needs in the market and a potential opportunity for a new entrant with the profile like LYBALVI. So on the next slide, you can see that we're getting ready to launch. The first half of 2021 is focused on driving awareness and planning for the launch. We will engage in scientific exchange with health care providers. We started a disease data education campaign last year, which we will continue through launch, and we'll continue our interactions with payers in the form of investigational product presentations. Based on our first-hand market insights, we've targeted a well-defined universe of physicians and systems for launch. The launch will leverage our existing organization, which is a significant asset and competitive advantage compared to standing up a brand-new commercial infrastructure at this time. We know that payers will impose restrictions to access at launch. That is not a mystery. This is something to plan for. We've designed patient access programs to help mitigate restrictions early in the launch, so patients can get LYBALVI as we work to improve access over time. So we'll be ready and looking forward to bringing forward this new medicine for patients. So let's move to the next slide and talk about what's coming next in the pipeline. On Slide 20, you see that our R&D is focused on developing high-value candidates in 2 therapeutic areas: neuroscience and oncology. Within neuroscience, we have a long-standing presence in psychiatry, which has expanded to include additional opportunities in neurology. Within oncology, we have platform capabilities in engineering cytokines. This is what led to nemvaleukin, and we've complemented that with small-molecule chemistry programs. We're excited to share more about these efforts later this year. In all cases, the threshold for nomination of new candidates has risen. Medicines need to have new distinctive properties representing true advances from existing standards of care. Moving to Slide 21. Nemvaleukin is our novel investigational drug designed to leverage the proven antitumor effects of the interleukin-2 pathway. Nemvaleukin is a stable, single polypeptide designed to selectively bind to the intermediate-affinity IL-2 receptor and expand tumor-killing CD8-positive and natural killer cells while having a negligible effect on regulatory T cells or Tregs. It was designed and developed internally by Alkermes scientists and represents a broader capability to engineer new molecules with attributes targeting established cytokine biology. Next slide. There's a good reason why a number of companies have pursued the IL-2 pathway. It's potentially a logical complement to a wide range of cancer treatments. IL-2 is a natural regulator of the activity of lymphocytes involving the immune response. You can see that in #3 in the diagram on the right. After cancer antigens are released and presented to the immune system, shown in #1 and #2 in the diagram, IL-2 drives the priming and activation of NK and CD8-positive cells. Expansion of these cancer-killing cells can heighten the body's natural immunological response to various tumor types. And the efficacy of many other cancer treatments depends on the robustness of this response. Its value as a target is already established. Recombinant human IL-2 is FDA approved. As monotherapy, it can drive complete and durable responses in certain tumor types, but its toxicity profile has significantly limited its broader use. A molecule with a differentiated tolerability profile, targeting the IL-2 pathway could be complementary to a wide range of other therapeutic approaches. Turning to Slide 23. We've taken a very disciplined, stepwise approach to developing nemvaleukin, and we've made a tremendous amount of progress. We think of the progression in these 4 sequential steps: first, confirm the validity of the molecular design through demonstration of the appropriate immunological response in humans; second, demonstrate that the immunological response translates into antitumor activity; third, identified the most expeditious pathway to initial registration; and then fourth, broaden the program to capture the full medical and economic value of the product. Next slide. We confirm the mechanism and set the groundwork for further development by demonstrating clinical pharmacodynamic response as measured by dose-dependent selective expansion of NK and CD8-positive T cells with minimum and non-dose-dependent changes in peripheral regulatory T cells. Then we advanced into the Phase II expansion stage of ARTISTRY-1 and ARTISTRY-2. Next slide. In 2020, we sought to confirm antitumor activity with the intravenous [Audio Gap] single-agent activity in melanoma is disclosed at ESMO last year and recently deserved a partial response in renal cell carcinoma. These represent the 2 indications for which recombinant human IL-2 is approved. Demonstrating single-agent activity is an important -- in our view, essential milestone for the program. We've also observed durable and deepening responses in combination with pembrolizumab in multiple tumor types, including in PD-1/PD-L1 unapproved tumor types. Moving to Slide 26. We're now focusing the program on initial registration pathways. As monotherapy, we intend to focus on mucosal melanoma. Mucosal melanoma is considered a particularly aggressive form of melanoma and is often not discovered until an advanced stage. Treatment options for this subtype of melanoma are very limited. In combination with pembrolizumab, we'll pursue platinum-resistant ovarian cancer, another area of unmet need with limited treatment options for patients. We plan to engage with FDA to advance our registration plans and initiate those studies this year. Next, as shown on Slide 27, we're now in the process of identifying and selecting additional tumor types and combinations to pursue in collaboration with others. This includes potential combinations with other agents, including IO agents, and other modalities as well as earlier lines of therapy versus standard of care. As the data set continues to strengthen, we see nemvaleukin as being an asset around which we can collaborate and create value. Turning to Slide 28. Our newest pipeline candidate is ALKS 1140, which is the first candidate nominated from our platform of selective HDAC inhibitor compounds. We are very excited about this biology. Inhibition of the CoREST HDAC complex provides a novel approach to potentially increase functional synaptic connections and synaptic integrity in the brain, synapses being the essential points of communication between neurons. This approach has potential applicability in a range of clinical settings, spanning from rare neurodegenerative and neurodevelopmental diseases to common psychiatric diseases. Next slide. As a reminder of what brought us to this area of research, synaptic loss is a pathologic correlate of the cognitive decline. Many neurological disorders are characterized by synaptic pathology. As a therapeutic target, improving synaptic number and function has the potential to slow progression and preserve cognitive and functional abilities in multiple disease states. The figure on the right shows the measurement of synaptic function in a healthy versus a diseased brain, in this case, a patient with schizophrenia. A simple graphic to make the point that there's a strong foundation of scientific understanding correlating synaptic function with functional status. Turning to Slide 30. ALKS 1140 selectively modulates the function of the CoREST HDAC complex. This complex exerts epigenetic control over synapse formation and function in the brain. The diagram on the right gives a hint to the challenge of the chemistry efforts. We're designing something more complicated than simply a small molecule inhibitor of HDAC 1 or 2. ALKS 1140 depicted as the small blue cluster inside the pink HDAC molecule is designed to inhibit the enzyme as it is complex with other regulatory proteins shown here as CoREST 1 and LSD 1. We had very clear goals for selection of a clinical candidate, focused on the appropriate selectivity and brain permeability, along with evidence of increasing synaptic density in preclinical models and designed to avoid the known potential hematopoietic side effects. We achieved these goals with 1140 and plan to begin the first-in-human studies in 2021. On to Slide 31. Nemvaleukin and ALKS 1140 are the most recent candidates to emerge from our research and development capability has been the foundation of growth of Alkermes since its inception. We have successfully developed many products. And along the way, we've evolved the scientific capabilities of the company to respond to the changing demands of competitive marketplace and the unmet need of patients. It's time to refresh your understanding of these capabilities and get a sense of other development programs we see emerging. So later this quarter, we'll host an Investor Day where we plan to share more details about these lead programs, nemvaleukin and ALKS 1140, and also provide more detail regarding the scientific platforms underlying them. Platforms that should continue to drive new innovation. We're excited about the discovery and preclinical programs that have been advancing in our labs in recent years. The science is compelling, and we're looking forward to introducing some of the scientists doing the work and sharing their progress. So on the final slide, we can finish where we started, with a focus on creating value in 2021. Our 3 focus areas are clear: grow and diversify our revenues; demonstrate the value of our R&D investments; and manage the company for growth and long-term profitability. I'll finish there, say thank you and open it up for questions with Cory.

Perfect. Thank you, Rich. And just as a reminder to our listeners that you have the ability to also submit questions via the conference portal and we'll work in as many as we can. We have some already. And welcome, Iain, here to the discussion as well.

Thanks, Cory.

All right. So I guess, Rich, let's start with the strategic value enhancement plan that you guys announced the end of last year in December. Kind of can you give us an overview of kind of the actions that you're taking and perhaps more importantly, why you're doing this and what you're really hoping to achieve here?

Sure. I think that it became clear to us that our investors were looking to us to be more explicit about the profitability goals of the company. And while we had a long-range plan that was consistent with that, we had not really been public about that at all. And there was a concern that we would continue to grow our revenues, but we would then continue to grow our expenses lockstep with it and really never drive profitability. So what we want to do is be much more explicit about that. And as you know, over the last couple of years, we've been actively refining the cost base of the company. A year ago, we restructured and took $150 million of expense out of the business. We continue that process this year as we, in some part, driven partially by COVID, but driving more efficiencies in the in the commercial side and focusing the R&D... So it became very clear that by putting explicit profitability targets out there, it would be helpful to people to see that we're going to continue to grow the business while growing the profitability as well. The other component of the plan is something that been ongoing, which is governance, updating the Board. We started that process a year ago, putting 2 new members on in 2020 and 2019. And putting more members on this year, 2 new members in '20, and we'll continue that process into 2021. That's an essential part to maintain the vibrancy of the oversight of the company as the business evolves and changes. And so I think going forward, this focus on assiduous management of costs against the backdrop of a growing revenue base should make people realize that we've got a very vibrant business that is more valuable than it's currently being valued at.

Okay. So I want to ask you a couple of questions on 3831 or LYBALVI as we're calling it now. With the PDUFA set in beginning of June, is there anything to read into the extent of the FDA review at this point? Because it didn't seem like there are any major concerns or issues that were there, and things have been resolved. So I thought maybe you could have a first quarter launch or pushing it towards middle of the year. Anything to read into that?

There's an industry-wide phenomenon going here in the wake of COVID as it relates to the FDA's ability to conduct pre-approval inspections. And so a number of sponsors have been delayed in their approvals by either the necessity for pre-approval inspection or in our case, this record review process that FDA uses that they have a regulatory authority to do. In fact, FDA put out guidance just recently saying that at records review, as they employ that, they will typically use a Class II resubmission status for that record response. So when we got the complete response letter around the PDUFA date, it was a very circumscribed question, a very simple question to answer, we answered it very quickly. They responded, "That was a complete response. Thank you very much. We're going to classify as a Class II resubmission and we have additional questions we want to ask you." So we see ourselves being in ongoing process of essentially answering the types of questions that you would have in a pre-approval inspection with the target date of June 1.

All right. And then for your actual launch plans, I mean, it sounds like you can leverage the existing sales force, which is obviously good. But can you talk about additional infrastructure you might need here? And maybe more importantly, how difficult is it to launch into such a generic marketplace balanced against the fact that you have relationships with a lot of these physicians, given your role with ARISTADA?

Yes. I think that 3831 is going to prove the point that we've been trying to make for the last couple of years, which is the ability to leverage the commercial infrastructure. I can't imagine how difficult it would be to launch a brand-new product and a brand-new commercial infrastructure in the midst of COVID into a generic market with so many systemic barriers to adoption of new products. We currently call on about 60% of the target audience that we would target for the launch of 3831. We currently have relationships with them via ARISTADA. And ARISTADA is the fastest-growing LAI in the market right now with an excellent positioning in this environment. So we have about 250 people in our psychiatry sales team out there right now, which is a substantial force. But even more importantly, Cory, is all the infrastructure that supports that. In terms of key accounts, national accounts, government pay, criminal justice, all the other elements, policy at state and federal level, we wrap around to bring these medicines to patients. So we will be able to launch 3831, LYBALVI, foundationally out of our existing infrastructure. And then we're going to add another 50-or-so people in terms of personal promotion and other digital resources to address a broader range of prescribers. But it's so interesting because a year ago at this time, if you would have asked us what that number would have been, we would have said 150 to 200 additional people. And that's what -- that's been the learning through COVID, is that psychiatry is one of the most rapid adopters of telemedicine. It actually makes sense in a lot of different territories, how much more efficient the telepsychiatry interaction can be both for the patient and for the rep calling on the doctor. So because we have existing relationships, it's much more easy to virtualize a relationship where we know each other. That's why you and I can have this conversation right now because we know each other over time rather than introducing ourselves this way. So we think that the combination of this hybrid model, personal promotion as well as digital, off this foundation of a very, very strong LAI presence with a drug like LYBALVI, whose primary offering to the marketplace is one of efficacy is a really strong foundation. And yes, the market is generic. That's table stakes. But as I mentioned in the presentation, 70,000 switches occur each month in bipolar I and schizophrenia, 70,000 each month because of the churn. So unfortunately, these patients are switching medicines all the time. They're relapsing, they're ending up in the acute setting and there's an opportunity for people to be introduced to and be put on a maintenance therapy with the efficacy of olanzapine.

All right. So last question on this front, at least for now. Given the existing infrastructure and those relationships, given the encouraging market research you have and the churn you just referred to, how do you think about that launch? And how is that balanced against the fact that you said it is a generic marketplace?

Well, there's a couple of things to think about in 2021 and not to try to make a virtue out of FDA's delaying, but launching during COVID is more difficult than launching not in COVID. So hopefully, as the year progresses and things re-equilibrate and settle down, and we're hoping that it doesn't get worse, and it may get worse before it gets better. But I think certainly, launching later in the year is not necessarily a bad thing. But I feel like that -- I'm sorry, Cory, repeat the essence of that question? Because I was...

Just thinking about expectations for launch, given all the parts.

So there's a lot of positives in there, but the mitigating features are access during COVID and just the natural shape of a launch curve during COVID. And number two is the fact that there are systemic impediments to adoption of new medicines. For example, there are a number of states on the order of 8 states or so where you won't have many restrictions, but there are probably 42 states where there are restrictions that might take we reckon over the course of a year to resolve. So you can hold these 2 ideas simultaneously. Number one is that the launch can be gradual, but that the overall market opportunity can still be very significant. And so we will actually pulse or stage our investment into the commercial expansion, consistent with the opening of different markets in different states over time. So you can imagine a calendar that begins over 12 months with the day the drug is approved and launched, and then how you're going to work through the impediments in various systems to gain access over that period of time.

Okay. Makes sense. All right. So let's move on to ALKS 4230 or nemvaleukin. So first, on the IV formulation, can you talk about the rationale for choosing platinum-resistant ovarian cancer for the combo therapy as you saw responses across a few different tumor types?

Yes. I think that, number one, it's an unmet need. It's a non-PD-1 approved tumor type, and we saw a very clear early signal in our ARTISTRY-1 program in that setting. So a lot of this is driven by investigator enthusiasm. And people see a real opportunity there. We -- remember, we see establishing a beachhead with first approvals in mucosal melanoma and platinum-resistant ovarian cancer. The ultimate promise of these IL-2 -- this IL-2 approach is its potential promiscuous combination across multiple agents and lines of therapy. So we want to start where we feel like we have the most clear, risk-mitigated and rapid pathway to approval. And that's why we've chosen the mucosal melanoma IV as monotherapy as well as the platinum-resistant ovarian cancer.

Okay. And then on the subcu front, when might we see updates from this part of the program, especially on the efficacy front? And how close are you getting to a recommended Phase II dose?

So we'll update at around the major medical meetings in 2021, and we'll probably give some insight at our Investor Day in Q1 as well. So we're progressing into the expanded phase of the subcu administration now.

Would that -- does the Investor Day, do you expect that to include data? Or is it more just kind of laying out the plan more so than anything else?

Okay. Again, we haven't settled on the executive agenda yet. But people will be hungry for data, if there's an appropriate update to give you.

Okay. And then as this all feeds into the potential for partnering nemvaleukin, how do you think about that? How critical of a role does getting some robust data around the subcu formulation play into it?

We thought about the accumulating data on nemvaleukin as building step-wise a series of milestones that confirm the idea that is an active agent, differentiated from the competition with real antitumor activity. And so the essential components of that were dose-dependent demonstration of the pharmacodynamic response that we wanted. It was consistent with the hypothesis, i.e. expansion of CD8-positive and NK cells without the corresponding expansion of Tregs, check. The demonstration, therefore, that the immunology translated into efficacy and not just efficacy in combination with checkpoint inhibitors, monotherapy efficacy. And as you know, Cory, we've going -- last time this year, we would have said that was a key deliverable in 2020 to prove that point. And had we not shown monotherapy efficacy, we would have been somewhat concerned. So check, and that's why this most recent RCC patient is confirmatory of that monotherapy efficacy. The third bit was to show that the subcu route was possible. We're testing in both once every 7 days and once every 21 days. That's a highly differentiated aspect of our program. So at SITC in the fourth quarter, we showed the dose-dependent pharmacology associated with the subcu. So the open -- the only open check box that we want to check to fully lay out this mosaic is that, that immunologic response subcu, like it did with IV, translates into efficacy, monotherapy and combination efficacy. We expect to check that box in 2021. Is that a necessary prerequisite to partnering? Yes and no. It's -- I think many people would tend to believe that the trajectory of the program is leading to that. There's no question that evidence of it would strengthen the bargaining. So we're not in a rush to partner. We're going to begin those interactions now. We feel like there's a substantial corpus of data now to talk about that's been published and presented in major meetings. So there's plenty to talk about. And we'll get a good sense of what potential partners are looking for.

Okay. Let me work in an audience question we have here on the commercial front is, how does growth of ARISTADA compare with ABILIFY MAINTENA? And what is the likelihood of a generic competitor for either one of these products and potential timing around that?

I think we're the fastest-growing, long-acting injectable in the marketplace right now. Interestingly, the overall LAI market growth, which has been healthy double digits for many years, it slowed down during COVID, as you might imagine, due to access to physicians and medication switch. But within that, ARISTADA is the fastest-growing of the LAIs. And we think it's because of the particular attributes that make it different than some of the others, namely this ability to initiate in the hospital without an oral run-in and then to discharge a patient with a 2-month dose. So there are others, a 3-month dose from a competitor. There's other long-acting doses, but those require stability first on the shorter duration dose. With ARISTADA, you can initiate with that 2-month dose. So I think that, that bodes well for it going into the new year. Iain can you provide more color on that?

No. I think from a patent perspective, our pattern extends into the 2030s. So we feel pretty strong from that perspective too.

Okay. Terrific. Well, with that, we are out of time. Thank you, both, very much for being with us today, and good luck with your meetings for the rest of the week.

All right, Cory. Thank you. Good luck.

Thank you, Cory.