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spk14: Greetings, and welcome to the Alkermes Third Quarter 2021 Financial Results Conference Call. My name is Rob, and I'll be your operator for today's call. If anyone should require operator assistance during the conference, please press star zero from your telephone keypad. Please note, this conference is being recorded. I'll now turn the call over to Sandra Coombs, Senior Vice President of Investor Relations and Corporate Affairs. Sandra, you may begin.
spk09: Thank you. Welcome to the Alkermes PLC conference call to discuss our financial results and business update for the quarter ended September 30, 2021. With me today are Richard Hopps, our CEO, Ian Brown, our CFO, Todd Nichols, our Chief Commercial Officer, and Greg Hopkinson, our Chief Medical Officer. Before we begin, I encourage everyone to go to the investor section of Alkermes.com to find our press release and related financial tables, including a reconciliation of the gap to non-gap financial measures that we'll discuss today. We believe the non-GAAP financial results in construction 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 report 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 statement. We undertake no obligation to update or revise the information provided on this call or the accompanying presentation as a result of new information or future results or development. After our prepared remarks, we'll open the call for Q&A, and now I'll turn the call over to Richard.
spk13: That's great. Thank you, Sandy. Good morning, everyone. So as we approach the end of 2021, I'm struck by just how much the company has evolved over the past year in the three areas we focused on so intensely, our commercial business, our R&D investments, and the pipeline. and the efficient management and governance of the company. On the commercial front, against the backdrop of an evolving pandemic, Vivitrol and Aristata continue to grow year over year, as the competitive positioning and attributes of these medicines have resonated with healthcare providers. For Vivitrol, a greater need for and growing acceptance of the use of medication to treat alcohol dependence has been a source of growth. For Aristata, its multiple doses and regimens continue to differentiate it from other long-acting injectable products. Libalvi has moved from the pipeline into the commercial portfolio. We launched Libalvi last week with a label that reflects its distinctive profile into a market that's characterized by large patient populations, significant unmet needs, and frequent treatment switches. We're launching Libalvi from an established and effective commercial platform, and we're well-positioned to capture operating leverage as the launch gains momentum. And continuing the positive momentum in the commercial portfolio, Vumerity has continued to demonstrate strong growth as Biogen drives uptake in the multiple sclerosis market. Vivitrol, Aristata, Lebalvi, Vumerity, all contributing to the top line. We've also continued to advance the pipeline. Nemvalucan has entered studies designed to support potential registration in mucosal melanoma and platinum-resistant ovarian cancer and has been granted fast-track designation in both of these tumor types. We've advanced our first selective HDAC inhibitor candidate, ALX1140, into first in human studies. ALX1140 presents an opportunity to harness the pro-synaptic effect of co-rest selective HDAC inhibitors and apply it to a range of neuroscience disorders. We've also recently nominated our orexin-2 receptor agonist, now known as ALX2680, and we're initiating IND-enabling activities. The biology of the orexin pathway has been validated in narcolepsy and we see a compelling opportunity in this space. Craig will provide further detail on these developments in a moment. And with respect to the efficient management of the business, you can see that our focus on growing revenue while concentrating R&D and SG&A investments in the areas of highest potential return and driving profitability is paying off. The impact of COVID is not over, but it's hopefully waning. I want to thank our remarkable teams in Ireland and in the U.S., for their incredible flexibility, resiliency, and dedication to the mission throughout. It's been inspiring to witness. So with that as a brief introduction, I'm going to turn the call over to Ian and Todd for a review of the third quarter financial and commercial results, followed by Craig with the pipeline. Ian.
spk03: Great. Thank you, Rich, and hello, everyone. We're pleased to report our third quarter financial results, which reflect our commercial execution and continued focus on expense management as we advanced our strategic business objectives. We delivered year-over-year top-line growth against the backdrop of the evolving COVID-19 pandemic. We focused our investment in operating expenses, which included both a $25 million development milestone related to the advancement of ALX1140 and preparations for the launch of Levolvi. And we are pleased to report robust non-GAAP net income for the quarter. Based on these results and our expectation of the treatment systems and markets for our products will normalize in the coming months. Today we are reiterating our financial expectations for 2021. Now let me start with an overview of our financial highlights. For the third quarter of 2021, we generated total revenues of $294.1 million, representing a year-over-year increase of approximately 11%. This was driven by the solid performance of both our proprietary commercial products as well as key products from our manufacturing and royalty business. We recorded a gap net loss of $29 million compared to a gap net loss of $0.1 million in the third quarter of 2020. Non-gap net income was $23.6 million for the quarter compared to non-gap net income of $41.5 million in the same period last year. Now, excluding the $25 million development milestone, we saw an improvement in the underlying non-GAAP net income year over year. For Vivitrol, net sales in the third quarter were $88.8 million, up 11% year over year, driven by a 7.5% increase in units, supported by the execution of our strategy to increase awareness and drive adoption of Vivitrol as a treatment option for alcohol dependence. Growth to net adjustments in the quarter of 52.3% were relatively consistent compared to 52.8% in the third quarter of last year. Inventory levels increased sequentially by approximately $1.5 million in line with increasing demand trends and typical seasonal patterns. Now turning to the Aristada product family, net sales in the third quarter increased 10% year-over-year to $68.9 million. driven by underlying unit growth of 10%. During the third quarter, growth to net adjustments for Aristada were 54.8% compared to 53.7% in the third quarter of last year. Now over the last year, fluctuations in channel inventory levels have resulted in lumpier Aristada quarterly net sales. While importantly, underlying total prescription trends have continued to increase quarter over quarter. For the third quarter, the sequential decrease in Aristada net sales from Q2 was primarily related to these inventory fluctuations. Recall that Aristada inventory in the channel increased by approximately 5,000 units or just over $6 million in net sales in the second quarter as a number of key customers adjusted their inventory levels to support growing demand. In the third quarter, inventory levels decreased slightly by just over a million dollars. Now, Todd's going to provide more insight into the underlying demand, which continued to grow sequentially on a TRX basis, despite a recent softening of the overall ALAI market, which we believe is COVID-related and expect to be transient in nature. Moving on to our manufacturing and royalty business, In the third quarter, our manufacturing and royalty revenues were $136.3 million, compared to $120.4 million in the prior year. This increase was driven primarily by accelerated uptake of Vumerity. Based on end market net sales, which increased to $121 million in Q3, we recorded $26.7 million of royalty and manufacturing revenues from Vumerity in the quarter, compared to $2.7 million in the third quarter of last year. Total operating expenses in the quarter increased by approximately $38 million compared to the same period in the prior year, driven primarily by the $25 million development milestone. R&D expenses for the third quarter were $118.4 million compared to $95 million for the prior year. Excluding the milestone, R&D expenses in the quarter were $93.4 million. Looking ahead, we continue to focus on efficient data-driven allocation of capital in our development portfolio as we prioritize and advance programs with the highest anticipated return on investment. SG&A expenses for the third quarter were $136.2 million, compared to $127.7 million for the prior year. This increase reflected incremental investment to support the launch of Levolvi, including the expansion of our psychiatry field sales organization in the quarter by approximately 50 representatives. Looking ahead, in line with our 2021 financial expectations, we expect that SG&A expenses will step up in the fourth quarter due to launch activities for Libolvi, which we're happy to report became commercially available last week. Turning to our balance sheet, we ended the third quarter in a strong financial position, with approximately $748 million in cash and total investments, and total debt outstanding of $296 million. Now as we look ahead, we're gonna continue to focus on driving operational efficiencies, leveraging our commercial infrastructure for a successful launch of Levolvi, and advancing our pipeline of development candidates as we seek to drive long-term value creation and profitability. And with that, I'll hand the call over to Todd.
spk08: Good. Thanks, Ian. And good morning, everyone. Our commercial performance in the third quarter for both Vivitrol and Aristata reflects year-over-year and sequential growth on a TRX and MBRX basis. This is particularly encouraging in light of the impacts we have seen in the markets for these medicines due to the resurgence of COVID-19 in certain parts of the country during the quarter. Aristata continued to be the fastest-growing, long-acting, atypical antipsychotic on a TRX monthly of therapy bases, and Vivitrol continued its momentum, driven by growth in the alcohol dependence indication. We also carried out our final preparations for the launch of Levolvi, our first oral antipsychotic, which I am pleased to say was made commercially available in the U.S. last week. We are leveraging our commercial organization and existing psychiatry sales force to bring this important new medicine to patients. I'll discuss the array of activities we are deploying to support our launch in a moment. But first, starting with Vivitrol. Net sales in the third quarter increased approximately 11% year-over-year to $88.8 million. Q3 Vivitrol unit demand continued to improve, driven by underlying prescription trends, despite ongoing pandemic-related disruptions to patient access and addiction treatment systems. We continue to be encouraged by increased adoption of Vivitrol in the alcohol dependence indication. Its overall prescriber breadth reached its highest level to date following a realignment of our healthcare provider targeting to focus on this indication. Based on our market research, a majority of healthcare providers that we surveyed in September reported an increase in the volume of patients seen for alcohol dependence compared to the prior month. The market data support this. Prescriptions for alcohol dependence treatments continue to grow at a faster pace than the overall addiction market in the third quarter. The recovery of total prescriptions for opioid dependence treatments since the height of the pandemic has been slower despite the ongoing opioid crisis. Certain settings of care, including residential treatment centers, have yet to fully return to their pre-pandemic operational capacity. We continue to believe that Vivitrol is an important and differentiated treatment option for opioid dependence and are focused on driving awareness and supporting healthcare providers and patients. Turning to our psychiatry franchise, which is now comprised of both Aristata, our long-acting injectable antipsychotic, and Levolvi, our newly launched oral atypical antipsychotic. For the Aristotle product family, net sales in the third quarter increased approximately 10% year-over-year to $68.9 million, driven primarily by TRX growth on a month of therapy basis of 15% year-over-year. This growth outpaced the broader long-acting atypical antipsychotic market growth of 6%. It's important to note that growth in the overall LA market has decreased from double-digit annual growth levels pre-pandemic. We believe this decrease is transient and related to the impact on prescription trends of fewer new patient starts and fewer treatment switches to injectable medicines during the pandemic. The value proposition and outcomes data supporting the use of long-acting injectables for the treatment of schizophrenia are clear, and we believe this class of medicines will continue to grow. While overall LAI market growth is an important factor underlying Aristotle's performance, Aristotle continued to be the fastest-growing LAI in the class during the third quarter on a month-of-therapy basis, and we believe Aristata remains well-positioned given its distinctive product attributes, including the Aristata initial regimen and the two-month dose. Aristata's position in the market provides a strong platform for the launch of Levolvi. This launch represents an important growth opportunity for us as we expand into a new market within psychiatry, and make this important product offering available to patients and healthcare providers. With Levolvi on the market, Alkermes can now offer both a long-acting injectable and an oral treatment option for schizophrenia, as well as an oral treatment option for bipolar I disorder. With our established commercial presence in the schizophrenia market with Aristata, we have an opportunity to leverage our commercial infrastructure and our capabilities and our existing relationships with healthcare providers and our market access expertise. In this early phase of launch, we are focused on three priorities, driving breadth of prescribing, generating new patient starts, and establishing payer coverage. We will be carefully monitoring performance against these three priorities. The most recent feedback from payers is consistent with our research over the last several years. Overall, we expect that Levolvi will be treated like other branded antipsychotic agents, and that its access profile will be established gradually over the next 12 to 18 months. Timing for coverage decisions will likely vary amongst our three main payer channels. We expect the decisions for commercial and Medicaid plans will be made available over the course of the next year, and the decisions for Medicare Part D plans may take up to 18 months. Importantly, there are pathways to access in each of these three channels as we await coverage decisions, and we are implementing programs to help support access for patients that are prescribed Libavi, such as our Libavi Care Support Program. Turning to our sales organization, last week, our sales representatives began actively engaging with healthcare providers, targeting approximately 22,000 prescribers who account for 80% of the branded prescription volume for schizophrenia and bipolar I disorder. Our Salesforce model is designed to support a competitive share of voice in the market for both Lubavi and Aristotle. Awareness levels for Lubavi have steadily increased since FDA approval. We launched Levolvi with a fully branded promotional campaign which we believe is advantageous as we educate the treatment community on the product attributes of Levolvi. We are also rolling out HCP educational programs as well as healthcare provider and consumer digital advertising to drive additional awareness of Levolvi. We are well prepared and ready for this launch. We are focused on execution and are excited to be engaging with healthcare providers and supporting patient access to Labavi as we drive awareness of this important new treatment option for people living with schizophrenia and bipolar I disorder. While we expect uptake to be gradual in the launch phase, we believe the market opportunity for Labavi is significant. I look forward to sharing updates with you in the quarters ahead. Now I'll turn the call over to Craig to review our pipeline progress during the third quarter. Thank you, Todd.
spk02: I'd like to start by saying how incredibly gratifying it is to see LaBelleVie now become commercially available to patients. The patients and caregivers that are impacted by schizophrenia and bipolar I disorder are a source of inspiration to us, and we are pleased to be able to offer this community a new treatment option that was designed with their needs in mind. Across our development programs, our objective is to develop innovative medicines with clear value propositions relative to current and anticipated future standards of care in neuroscience and in oncology. We've made significant progress in our pipeline this year, starting with Nembolucan, our novel investigational engineered IL-2 variant immunotherapy. Nembolucan has demonstrated durable and deepening responses in a range of tumor types, both as a monotherapy and in combination with pembrolizumab in CPI-naive and CPI-experienced patients. Our clinical development strategy is designed to address key unmet needs in the field and focused on difficult to treat patient populations, including patients with checkpoint inhibitor unapproved tumor types and imposed checkpoint inhibitor settings. Nembolucan is entering studies designed to support potential registration in two such tumor types with significant unmet need. First, mucosal melanoma, a rare and aggressive form of melanoma that has limited treatment options. Earlier this year, FDA granted Nemvalucan orphan drug and fast-track designation for the treatment of mucosal melanoma, underscoring its potential clinical utility for patients with this disease. Based on objective responses and disease control seen in Autistry 1 in this difficult-to-treat tumor type, we initiated Autistry 6, a Phase II monotherapy study designed to support potential registration. This study is expected to enroll approximately 70 patients with mucosal melanoma who have progressed on checkpoint inhibitors and who will be treated with IV nevalucan. This study is also expected to enroll approximately 40 patients with cutaneous melanoma who will receive once weekly subcutaneous nevalucan as we continue to evaluate that route of administration. The RS36 study is designed to build on the clear monotherapy signal that we've seen for the IV nevalucan in checkpoint inhibitor experienced patients. which we believe is an important differentiator in this space. In the clinical development program, we've also observed encouraging anti-tumor activity with IV and involucin in combination with pembrolizumab in patients with platinum-resistant ovarian cancer. In a disease where the progression-free survival associated with standard of care in the post-platinum setting is approximately three and a half months, we've been particularly encouraged to see our patients in auditory one experience durable clinical benefit. Earlier this week, FDA granted fast-track designation to the combination of Nemvalucan and Pembrolizumab in platinum-resistant ovarian cancer, and we announced the initiation of Artistry 7, a global phase 3 open-label randomized trial evaluating the anti-tumor efficacy and safety of IV Nemvalucan in combination with Pembrolizumab compared to investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian fallopian tube or primary peritoneal cancer. The primary endpoint of Artistry 7 is investigator-reported progression-free survival based on RESIST 1.1. The study is expected to enroll approximately 376 patients who will be randomized to one of four treatment arms to receive nevalucan and pembrolizumab combination therapy, pembrolizumab monotherapy, nevalucan monotherapy, or investigator's choice chemotherapy. R3-7 is being conducted in collaboration with Merck under a clinical trial and supply agreement for Pembrolizumab. We've also entered into agreements with two preeminent collaborative groups in gynecological oncology, the GOG Foundation and the European Network of Gynecological Oncological Trial Groups to conduct the study. We're in the process of initiating the clinical trial sites and expect to begin patient dosing early next year. Based on the activity that we've seen in our current IV dosing regimen, including the durability of some of the responses observed, and consistent with our patient-centric focus, we also plan to explore the potential for less frequent intravenous dosing options. Currently, in our ongoing IV studies, patients receive a 30-minute Nembolucan infusion in an outpatient setting for five consecutive days, followed by a 16-day off period. This regimen has demonstrated anti-tumor activity both in monotherapy and in combination with pembrolizumab in multiple tumor types, and clinicians believe this is an acceptable dosing regimen. A less frequent dosing regimen may offer additional flexibility to patients, which may be useful as we consider additional tumor types and potential combination regimens. Based on extensive modeling and the PKPD safety information that we've collected in clinical studies to date, We plan to add evaluation of once every three week and twice every three week IV dosing intervals to our clinical program starting in the first quarter of 2022. We're also continuing to evaluate weekly subcutaneous dosing in the ongoing Artistry 2 study and in Artistry 6 as I outlined earlier. For Artistry 2, the dose expansion cohorts are ongoing and we will identify appropriate medical meetings at which to present those data next year. As we look ahead, we believe there are a variety of tumor type combinations and lines of therapy for which Nemvalucan may have potential clinical utility. We are now well-positioned to advance Nemvalucan towards potential registration in mucosal melanoma and platinum-resistant ovarian cancer, and will consider additional tumor types and clinical work going forward in the context of potential partnerships. Turning now to ALK1140, our selective HDAC inhibitor candidate. Many neurological disorders are characterized by synaptic pathology with synapse loss, abnormal density of dendritic spines, and aberrant synaptic signaling and plasticity. For these disorders, targeting the synapse may slow progression and preserve cognitive and functional abilities. We are pleased to have recently initiated our first in-human study and expect to complete single and multiple ascending dose studies in 2022. These studies are intended to confirm brain penetration and determine the PKPD and safety profiles of ascending doses of ALX1140 in healthy volunteers. Biomarker from these studies may also provide proof of target engagement for this novel molecule. In parallel to the first in human studies, we plan to conduct a phase zero biomarker program to inform indication selection and clinical study designs. We are considering a number of psychiatric, neurodegenerative, and neurologic indications for ALK1140, and we'll continue to refine our approach to indication selection as we advance in the clinic. ALK1140's biology may have utility in a number of different areas, and we are carefully considering which potential indications may offer the highest likelihood of clinical, regulatory, and commercial success. Moving to our REXN2 receptor agonist. We recently nominated ELKS 2680 to advance towards the clinic. This candidate nomination triggered the initiation of IND-enabling activities necessary to support the first in human studies. Consistent with our strategy to apply innovative molecular design to development programs with a strong biologic rationale, but that presents technical design challenges, our goals for 2680 was to design a novel molecule that is selective for the REXIN2 receptor. has favorable half-life with a pharmacokinetic and pharmacodynamic profile that mirrors the natural sleep-wake cycle and aims to avoid certain safety risks associated with existing stimulant medications. Data from a preclinical model, which serves as a predictive disease model of narcolepsy in humans, demonstrated dose-dependent increases in wakefulness and dose-dependent decreases in cataplexy with ALKS2680. The pharmacokinetic and pharmacodynamic relationship for ALKS2680 observed in our preclinical work has also suggested the potential for a low human dose and drug burden, which may be important for safety and tolerability. Importantly, at pharmacologically relevant plasma exposures in a preclinical rat hemodynamic model, ALKS2680 did not adversely elevate heart rate or blood pressure, two key safety parameters related to the erection pathway. We are excited about this program and currently expect to enter the clinic in late 2022 or early 2023, following the completion of IND enabling activities. Taking a step back, as our molecules advance through the various stages of development, we are continuously interrogating and addressing key critical questions. With defined stage gates designed to enable data-driven decision making, we believe that we are well positioned to continue to advance our pipeline and efficiently allocate capital. I look forward to sharing our progress with you, and I'll turn the call back over to Rich.
spk13: That's great. Thank you, Craig. The progress we've made across the business is substantial. We have a clearly defined strategy that we believe has the potential to advance important new therapeutic treatment options in neuroscience and oncology and drive meaningful value creation for our shareholders. So with that, I'll turn it back to Sandy to run the Q&A.
spk09: All right. Thanks, Rich. Rob, we'll now open the call for Q&A, please.
spk14: Thank you, Sandy. If you'd like to ask a question at this time, please press star 1 from your telephone keypad, and the confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants that are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions.
spk15: One second, that's star 1. Thank you. Our first question is coming from the line of Femil Devon with Mizuho Securities.
spk14: Please proceed with your questions.
spk01: Great. Thanks for taking my questions and the info on the call. So maybe just a couple follow-up questions on stuff you discussed. So one, on Aristotle, I appreciate the comments regarding the market dynamics and some of the slowing using maybe COVID-related. Can you just talk a little bit about sort of gross to net expectations? It bounced up again a little bit in this past quarter relative to last year. Maybe you can just talk about sort of how you're thinking about that for fourth quarter or kind of for 2022. And then on Lybalvi, again, appreciate your comments regarding the initial payer feedback. I think one question we frequently get is just sort of the expectations around the need for patients to potentially have to take a generic olanzapine before they're given access to Lybalvi. So I'm wondering if you can just sort of clarify your latest expectations there in terms of access now that the product's on the market. Thank you.
spk03: Yeah, thanks, Pamela. Let me just kick off with the growth to net question around Aristada. I think as we've looked at Aristada over the course of 2021, the growth to nets have actually been relatively consistent. They were 54.8% in both Q2 and Q3 this year. So we believe that that's an appropriate level that's going to continue into the future. It obviously depends on mix. We have had a slightly higher Medicaid utilization in 2021 as compared to 2020, which has caused the year-over-year increase, but we think that we're relatively consistent around 55% going forward.
spk08: Yeah, good morning. This is Todd. I'll take the question on Levalvi Pair Access. We're really excited about the launch last week. You know, it's the first week, and we're very encouraged by this. We are seeing that payers are beginning to make initial coverage decisions. This means medical exceptions, prior authorizations, and step edits. But this is consistent with what we expected and what we've learned over our research over the last couple years. And what we are seeing, along with our expectations, is there is a pathway to access across the three different channels. Claims are being adjudicated in a variety of plans right now. So we don't have specifics on if they're stepped through a Lanzapine at this time, but knowing how the branded category works, how payers have told us, there will be step edits in place. It could be one or two generics. There will be medical exceptions in place, and there will be prior authorizations in place. As I said in my prepared remarks and as in the past as well, the access profile will be developed and will reveal itself really over the next 12 to 18 months.
spk01: Okay, thank you.
spk14: Our next question is from the line of Akash Tiwari with Jefferies. Please receive your questions.
spk05: Hey, thanks so much. So a couple. One, what's your take on the recent discontinuation of the TAC-994 program? Do you think it could be related to their metabolism or metabolites, or do you think that unexpected AE could be an on-target effect? Also, you mentioned that your program preclinically didn't show increases in blood pressure and heart rate. wouldn't that be considered an on-target effect for Ox2? And then secondly, can you go over the approximate cost for the artistry six and seven study? And stepping back, where do we stand with the aisle two program from a capital allocation perspective? Would you commit to ending your spend for the aisle two program by 2023 if a suitable partner isn't found? Thanks so much.
spk02: Yeah, thanks for the question. I'll address the erection question. You know, Takeda didn't give much detail in terms of the safety event or events that they saw in their program. It seems as if it may be an off-target effect. And you're right, you know, in terms of the blood pressure and heart rate that we extensively examined in our rat hemodynamic model, that would be viewed to be an on-target effect, but these are important events that occur with stimulant medications, and we wanted to make sure that we weren't seeing any of those effects with 2680. We've also performed a rat EEG model with our compound and believe that our predicted human dose is going to be low, and so we're pretty confident in the preclinical safety profile that we've generated to date, and our next steps are now to move into IMD enabling activities for the program.
spk09: Akash, I missed your question on artistry six and seven. Could you repeat that, please?
spk05: Yeah, absolutely. So what are the approximate costs for both of those studies? And then kind of stepping back from a capital allocation perspective, would you be able to commit to ending your spend for the IL-2 program by 2023 if a suitable partner isn't found? Thanks.
spk03: I think from a capital allocation perspective, with the IL-2 program, we're going to be continuing in mucosal melanoma and PROP. Those are two registration studies that we believe that we can proceed with and we can ultimately land. We would only look at potentially expanding the program in the event that we found a suitable partner.
spk13: Yeah, gosh, it's rich. So in the scenario, which we don't think is the planning scenario, but we plan for it anyways, if we had no additional support on the program, we would go to the finish line on Artistry 6 and 7. primarily because of the clinical signal that we're seeing with IV nebulucan in these patient types. These are real unmet medical needs. There's real interest in the program from investigators because of the quality of the signal that we've seen in these indications. And just to be clear, these are unmet needs. These are places where, in the case of mucosal melanoma, there are limited treatment options. And in the case of PROC, This is actually a checkpoint in unapproved tumor type where we're seeing evidence of durable responses in certain cases in combination with Nembolucan. So I think there's a compelling both commercial and medical need for us to get to the finish line. Our hope is to be able to expand the program in the context of partnerships based on meeting the design criteria that we designed for Nembolucan at the outset.
spk14: Thank you. Our next question is from the line of Corey Kasimov with JP Morgan. Please proceed with your question.
spk04: Hey, good morning, guys. Thanks for taking my questions. Two for me as well. So first on Mabalvi, recognizing you just launched this last week, I'm just wondering if you have a sense from your prior physician education and initial interactions, if there's any way to delineate the interest in these early days between schizophrenia and bipolar, or if you expect it to be Pretty similar between the two. And then second question, just wondering if there's an interim look built into Artistry 7 in platinum-resistant ovarian cancer. Thank you.
spk08: Hi, Corey. It's Todd. Appreciate the comment. You know, the profile over the first week here, the clinical profile is being well-received. So we're really encouraged with that. It's very consistent with the research we've done over the last couple of years, and the value proposition is starting to resonate. You know, ACPs are telling us that the broad indications and the utility for the different patient types are very interested to them. So we don't have data at this point, specific data, on the type of patients, but the interest that we're hearing from ACPs is specific around the switch market. You know, patients are thinking about switching to branded agents for efficacy, tolerability, or safety, schizophrenia, and bipolar. So we're actually hearing all three categories at this point. But we don't have anything specific at this time. I think over the next several quarters, we'll start to see some of the patient claims data and can provide more specificity at that time.
spk02: Hi, Corey. And with regards to your question on Artistry 7, we haven't discussed the inclusion of any interim analysis in the study design at this point in time. You know, obviously, even though this is an open-label study, we won't be – allowing the team to take a look at the data and we'll be keeping our teams blinded to the aggregate data throughout the conduct of the study. Okay, thank you.
spk09: Thanks, Corey.
spk14: Our next question coming from the line of Brandon Foulkes with Cantor Fitzgerald. Please receive your question.
spk06: Hi, thanks for taking my question. I just want to talk about Vivitrol and the alcohol opportunity here. I think it's been a few quarters now. where you've messaged about focusing on that opportunity. Given the size of that opportunity, how should we think about the timeline for capturing maybe this tailwind in sort of three, five years, given you are changing the treatment paradigm a little bit here towards these medication-assisted treatments? And then given the large opportunity here, you know, you are making headwinds, but just Any color in some of the prescribing questions you're getting around moving the alcohol treatment paradigm towards Vivitrol? Thank you.
spk08: Brandon, hey, yeah, this is Todd. Let me take that as well. We're really encouraged by the adoption and utility for Vivitrol and alcohol dependence. If you look at the overall total market right now, we really see this as two distinct markets, alcohol dependence and opioid dependence. The overall market right now is being driven by performance and growth within an alcohol dependence market, and we're starting to see some stabilization post-pandemic or during the pandemic here for opioid dependence. We are seeing physicians consistently, when we think about the opportunity in our market research, physicians are telling us that they're actually seeing increased patient flow within alcohol dependence, that they believe that more patients are originating in their offices, mainly outpatient, for alcohol dependence, and that's a really good place for Vivitrol to play at this point. So the way we're looking at this is from multiple different metrics. TRX market growth for alcohol dependence is growing at about 15% year over year versus opioid dependence is about 1% to 2%. And Vivitrol is actually showing similar trends, you know, double-digit growth. And then when we look at new patient starts right now, For the overall market, the market is growing at about 12% right now, and Vivitrol with an alcohol dependence is growing north of about 20% right now. So we see some very encouraging trends. We see adoption with an alcohol dependence to be a big opportunity long term. The significant opportunity is really in penetrating the addressable patient population. Again, there's 14 million Americans that actually have alcohol dependence. there's only about 400,000 that are on treatment. So our focus right now strategically is building awareness and then making Vivitrol an option for those patients. So we do see this as a long-term growth opportunity for the brand.
spk06: Great. Thank you very much.
spk14: Thank you. Our next question is from the line of Mark Goodman with SVB Laring. Please proceed with your question.
spk12: Yes, good morning. In the press release, you talked about if you don't see an improvement in kind of the system in the quarter, you could not meet expectations. Can you just give us a little more color on that, how sensitive the revenues are to what your commentary is? And I guess we're well into at least one of the months. Maybe you can comment on how that's been going. Second of all, Just a follow-up, aristotic gross to net, a commentary around 55%. Were you referring to the rest of the year? Or were you referring to how we should be thinking about it next year and the year after? And the reason I ask is just because, obviously, the gross to net has been going up so fast over the past couple of years. So I was just wondering if you feel like we finally got to a place where we're capping out. And then lastly, just 1140, I know you haven't picked an indication yet, but can you just give us a sense of a few of the indications you've narrowed it down to? Thanks.
spk03: So I'll kick off there, Mark, if I can. So I think with regard to our financial expectations for the year, we were pleased with the progress we've made during the course of the year. We improved our expectations on the July call, and we're happy to be able to reiterate those on the call today. I think with respect to Vivitrol, we're very well placed with the guidance range that we have. that with respect to Q4, we still anticipate coming in the middle of that range. And on the Aristata side of things, as Todd mentioned, we have seen a softening in the ALAI market. But even with that said, we anticipate the guidance range that we went out with in July still being appropriate for that business. On the Aristata growth to net question specifically, I think we have seen a steady increase in gross to net. I think all things being equal, we have seen over the last few quarters that gross to net has kind of evened out. For the year, we're at 54.4%. The last two quarters have been 54.8%. So with the market currently constituted as is, I would anticipate that, you know, we would see a 55% gross to net as we go forward. You know, obviously there are a few things potentially going through Congress from a pharmaceutical pricing perspective which could impact that but all things being equal I think 55% is a good way to model gross to net going forward for Aristotle Yes, so in terms of 1140 where we're initiating our
spk02: first in human studies in Australia at the moment. We've got patients in screening in that program. And we're taking a mindful and stepwise approach to indication selection. We believe that there are a number of potential indications which are of interest to us, some of them psychiatric, others neurodegenerative, and others that are more on the pure neurology side of things. At this point in time, we're going to be running phase zero studies, which would inform biomarkers of synaptopathy, neurocognitive function, and we believe that those phase zero studies will help us refine our indication selection as we move forward as well and inform proof of concept studies and which biomarkers we will include in those proof of concept studies as we move forward.
spk15: Thank you.
spk14: Our next question is from the line of Umar Rafa with Evercore. Please use your questions.
spk10: Hi, guys. Thanks for taking my question. I had three different topics today, if I may. Perhaps first, as I think about Lybalvy, one of the considerations I've been trying to think about is what percentage of the target population in schizophrenia and in bipolar has a substance abuse problem? And I ask because I'm curious how clinicians and patients who do have a substance abuse problem, how are they reacting to the antagonist in Lybalvy, number one? Secondly, on aisle two, I recall you all were updating response rates as they were coming in, including at broker conferences, and we haven't heard much on responses in several months now. Should we perceive that as a lack of responses, or are you just accumulating data for a more holistic update, perhaps at an ask or something? And then finally, on 1140, if you could just remind us what the heme tox profile is on this molecule. as well as what's the sort of preclinical data differentiation versus the prior lead 929. I asked because Rodin had said 929 had mirrored the preclinical data, but the program was dropped and there was never any clarity, especially because the company was private on what actually happened on 929. So some of that background would be very helpful on 1140. Thank you.
spk08: I'll start first with LaValle. You know, the We looked at this multiple different ways. If you look at the epi data, IQVIA reports also as well that about 4% to 8% of patients in this category, schizophrenia and bipolar, also are on opioids as well. So we talked to physicians a lot about this to make sure that there's clarity on how to identify those patient types and then where would Lebalvi be positioned. And physicians tell us consistently in our research that they're able to identify those patients. So we don't see that as a barrier to access or a barrier to acceptance as well. We also hear very encouraging feedback, even most recently since the approval of LaBalvie, on the weight metabolism potential effects of using a product such as samudorphine in combination with a well-established agent such as olanzapine right now as well, too. So there is interest in the clinical community, as you know. We actually have nine studies that were used for the approval specific to samudorphin, and it is a high interest in the medical community at this point.
spk02: Yes, and then with regard to the question on IL-2, we did an extensive update on Autistry 1 and Autistry 2 at ASCO. We updated on the melanoma population at ESMO in our Autistry 6 trials in progress post-ASCO. We did increase enrollment in the melanoma cohort, and at this point in time, we're waiting for data to mature, and we'll look to present at appropriate conferences next year. With regard to the question on 99, our approach with our HDAC program is really to design compounds that are devoid of the hematological toxicity, which in our preclinical studies has been confirmed. So the preclinical profile has confirmed that. With regard to Rodan's 929 program, although it did provide interesting data on the profile as it relates to safety and tolerability and the pharmacokinetic and target engagement of these selective HDAC inhibitor complexes, we believe that 1140 has superior properties to the 929 candidate, and that's why we've decided to move that into the clinic and move forward with that as our lead compound now.
spk14: Thank you. Our next question is from the line of Paul Matisse with Stifel. Please resume with your questions.
spk07: Hey, thanks so much. I just have one question on Lebalvi. And actually, one quick follow-up on just pandemic-related impact on commercial. So on the Baldy, I guess from a modeling perspective, it's challenging because there's so many olanzapine scripts every year, and some people, it seems, use comps. Do you view any of the recent atypical launches as kind of a reasonable comp to actually gauge the success of this launch against? And then separately, I was just curious, in the past few months, what percent of your interactions with doctors are in-person versus, say, six months ago? Thanks so much.
spk08: Good morning. This is Todd. I'll take the last part of that question. First, Paul, we're seeing improvements in in-person engagements. Right now, it's approximately 70% of all of our engagements for our sales forces in person. That's up from 40% at the beginning of the year. So we continue to see improvements in that area. And in fact, in some of the research that we conduct, greater than 50% of physicians tell us they prefer in-person engagements. And they really prefer in-person engagements, especially when you have a product launch. So we think that's a strategic opportunity for us to leverage our commercial infrastructure for the launch of Labavi. To your point around, you know, just overall TRXs as well, too, you know, Olanzapine is really well established in the marketplace, mainly because of the efficacy that it provides. When you look at bipolar I disorder and also schizophrenia, you're looking at about four and a half to 5 million TRXs on an annual basis. So it's a really large market opportunity that's growing. Physicians tell us that that could be a source of business over time. So we think with a large penetration of olanzapine, as you know, olanzapine holds approximately a 13 share overall in the marketplace, and it is growing as well based upon its efficacy attributes that Levolvi would be very well received within that physician population.
spk07: Any thoughts on comps?
spk08: Oh, comps, yeah, absolutely, Paul. So probably the most recent comp is a good one to look at. You know, product launches over the pandemic are challenging in general as well, but the most recent launch, Lumeteperon, would be a good one to look at overall. But as I said in my prepared remarks, we do believe that based upon the market dynamics right now that the launch will be gradual over time, but we think the market opportunity is just enormous. You know, it's over a $3 billion market. opportunity within the branded space, and we believe that LaValle is going to compete very well in the branded market conditions.
spk07: Cool. Thank you very much.
spk09: Thanks, Paul. Rob, we have time for one more question, please.
spk14: Hey, the question will be coming from the line of Jason Gerbery with Bank of America.
spk11: Hey, guys. Good morning. Thanks for taking my questions. So, first one is just... Curious, does the agreement with Elliott require you guys to hit any profitability margin threshold in 2022? I ask just because I'm looking at consensus, which has OPEX growing pretty negligibly, and it's a new product launch year for you guys. So just sort of curious if you can comment directionally, not asking for guidance, but just how you guys, how we should be thinking about that. And then on IL-2, maybe a question for Rich. What incrementally do we need to learn about sub-Q format from here to get to that de-risking threshold that you've talked about in the past that would facilitate partnership discussions? And does it maybe entail accruing more clinical data to mirror or replicate what we see with IV? Thanks.
spk03: So maybe I'll take the first part of that question, Jason. So there are no profitability targets agreed with Elliott for the 2022 timeframe. We are obviously committed to the profitability targets in 23 and 24, and we'll be managing the business in order to be able to hit those targets.
spk13: And, Jason, on that final question, yeah, I think more data is always better, and we're already seeing the impact of that this year compared to last year with respect to discussions we're having with potential partners. With Nembalucan moving into registrational enabling studies in both monotherapy, which is distinctive, as well as in combination with PEMBRO, importantly, in PEMBRO-unapproved tumor types. We're opening new white space. SubQ is a really interesting differentiating feature, but you heard Craig say today, based on the quality of the emerging signal in IV, we've also decided to introduce less frequent IV dosing as well, because remember, that first IV dosing schedule, which to remind you, is daily IV for five days, followed by 16 days of rest, That's a perfectly acceptable schedule in these unmet needs, but that's based on the original proleukin dosing schedule. Our modeling and that whole modeling capability has gotten so much more sophisticated than back in those days. We're quite confident that there could be more economical IV dosing regimens as well. So sub-Q, less frequent IV, and mainstay IV, three legs of the stool to support the efficacy that we're seeing.
spk11: Got it. Thank you.
spk09: Great. All right. Thanks, everyone, so much for joining us on the call this morning. Please don't hesitate to reach out to us if there are any follow-up questions. And we'll look forward to speaking to you again in February.
spk14: Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.
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