Q4 2019 Earnings Call

Greetings and welcome to the Alkermes fourth quarter and year end 2019 financial results Conference call.

Rob: Greetings and welcome to the Alkermes fourth quarter and year-end 2019 financial results conference call. My name is Rob, and I'll be your operator for today's call. If anyone should require operator assistance, please press star zero on your telephone keypad.

My name is Robin I'll be your operator for today's call.

If anyone should require operator assistance. Please press star zero from your telephone keypad.

Sandra Coombs: Please note, this conference is being recorded. I'll now turn the call over to Sandy Coombs, Vice President of Investor Relations. Sandy, you may begin. Thank you.

Please note this conference is being recorded.

I'll now turn the call over to Sandy Cold Vice President Investor Relations, Sir you may begin.

Thank you good morning, welcome to the Alkermes plc conference call to discuss our financial results at business update for the quarter. In your ended December 30, 129 team with me today or Richard Parkes their CEO, Jim freight either CFO, Jim Brown, our SVP of finance before we begin I encourage everyone to go to the Investor section of Alchemy Dotcom.

Sandra Coombs: Good morning. Welcome to the Alkermes Plc conference call to discuss our financial results and business update for the quarter and year ended December 31, 2019. With me today are Richard Pops, our CEO; Jim Fradies, our CFO; and Iain Brown, our SVP of Finance. 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 GAAP to non-GAAP financial measures that we'll discuss today. We believe the non-GAAP financial results, in conjunction with the GAAP results, are useful in understanding the ongoing economics of our business. Our discussions during this call will include forward-looking statements. Actual results could differ materially from these forward-looking statements. Please see slide two of the accompanying presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements.

Despite our press release and related financial table, including a reconciliation of the GAAP to non-GAAP financial measures that will discuss today.

We believe the non-GAAP financial results in conjunction with the GAAP results are useful in understanding the ongoing economics of our business.

Our discussion during this call will include forward looking statements actual results could differ materially from these forward looking statements.

Please see slide two of the accompanying presentation. Our press release issued this morning, and our most recent annual and quarterly reports filed with the FCC for important risk factors that could cause our actual results to differ materially from those expressed or implied in forward looking statement.

Sandra Coombs: Our prepared remarks today will include preliminary data from the Artistry Clinical Program. These data may change as patient enrollment continues and as more patient data becomes available. It may not be indicative of final data from such trials or results of future clinical trials. We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or developments. After our prepared remarks, we'll open the call for Q&A. Now, I'll turn the call over to Jim.

Our prepared remarks today will include preliminary data from the artist preclinical programs. These data may change of patient enrollment continues and is more patient data becomes available and may not be indicative of final data from such trial or result of future clinical trial, we undertake no obligation to update or revise the information provided on this call or in the accompanying presentation at the.

Result, at new information or future results or development.

After our prepared remarks, well open the call for acuity now I'll turn the call over to Jim.

Jim: Thank you, Sandy. In 2019, we achieved a billion dollars in revenue for the second consecutive year. The second half of the year was particularly active for us. We saw the addition of a new revenue stream with the approval of Vumerity and set the stage for the potential addition of another revenue stream with the submission of our NDA for ALKS3831 for the treatment of Schizophrenia and Bipolar I Disorder. We implemented a restructuring in the fourth quarter that recalibrated our cost structure and focused our R&D investments in programs with the highest potential value, and we acquired Rodin Therapeutics, which further diversified our pipeline. I'll start with an overview of our key financial and commercial highlights.

Thank you Sandy.

In 2019, we achieved a billion dollars in revenue for the second consecutive year.

The back half of the year was particularly active for US. We saw the addition of a new revenue stream with the approval of Verde and set the stage for the potential addition of another revenue stream with the submission of our India for Alex three Athree, one for the treatment of schizophrenia and bipolar one disorder.

We implemented a restructuring in the fourth quarter that recalibrated, our cost structure and focused our R&D investments in programs with the highest potential value.

And we acquired Rodin therapeutics, which further diversified our pipeline.

I'll start with an overview of our key financial and commercial highlights.

Jim: For the full year 2019, total revenues grew 7% year over year to $1.17 billion, and we recorded non-GAAP net income of $112.2 million, which was ahead of our expectations. For the fourth quarter, we recorded total revenue of $412.7 million and non-GAAP net income of $131.4 million. These results were driven by growth in proprietary product sales, continued strength of our base royalty and manufacturing business, and the receipt of the $150 million milestone payment from Biogen related to the approval of Umeri. Vivitrol net sales in the fourth quarter increased 11% year over year to $92.8 million, driven primarily by 14% unit growth. Vivitrol experienced solid growth in key states such as Arizona, California, and Texas and broad-based growth in states with a lower Vivitrol share, with 19 states growing more than 25% year over year.

For the full year 2019, total revenues grew 7% year over year to $1.17 billion and we recorded non-GAAP net income of $112.2 million. There was ahead of our expectation.

For the fourth quarter, we recorded total revenue of $412.7 million non-GAAP net income of $131.4 million.

These results were driven by growth of our proprietary product sales continued strength of our base royalty and manufacturing business and the receipt of the $150 million milestone payment from Biogen related to the approval of were married.

Vivitrol net sales in the fourth quarter increased 11% year over year to $92.8 million, driven primarily by 14% unit growth.

David for all experienced solid growth in key states, such as Arizona, California, and Texas and broad based growth in states with lower Vivitrol share with 19 states growing more than 25% year over year.

This growth was Pos partially offset by an increase in gross to net adjustments of 47.7% as compared to 46.3% in the fourth quarter of 2018.

Jim: This growth was partially offset by an increase in gross to net adjustments of 47.7% as compared to 46.3% in the fourth quarter of 2018. However, sequentially, Vivitrol net sales grew 9% compared to the third quarter of 2019, driven by 7% unit growth and slightly lower growth to net adjustments, driven largely by payer. For the full year 2019, Vivitrol net sales increased 11% year over year to $335.4 million, driven by unit growth of 12%. Gross net adjustments for Vivitrol were 48.3% for the year, relatively flat compared to full year 2018. Turning to the Aristata product family, for the fourth quarter, net sales increased 16% year-over-year to $56.8 million, driven primarily by unit growth of 24% and partially offset by higher growth-to-net adjustments of 50.7% compared to 43.5% in the fourth quarter of 2018, due to payer mix and the addition of Aristotle to the formulary at the VA. Sequentially, Aristotle net sales grew In December 2019, Aristata's market share for new prescriptions in terms of months of therapy was 32% in the long-acting aripiprazole market and 9% in the overall market for long-acting atypical antipsychotics.

Sequentially Vivitrol net sales grew 9% compared to the third quarter of 2019, driven by 7% unit growth and slightly lower gross to net adjustments driven largely by payer mix.

For the full year 2019, Vivitrol net sales increased 11% year over year to $335.4 million driven by unit growth of 12%.

Gross to net adjustments for Vivitrol were 48.3% for the year relatively flat compared to full year 2018.

Turning to the Aerostar product family for the fourth quarter net sales increased 16% year over year to $56.8 million, driven primarily by unit growth of 24% and partially offset by higher gross to net adjustments of 50.7% compared to 43.5% in the fourth quarter 2018.

Due to payer mix and the addition of the aerostar bare stada to the formulary at the DJ.

Sequentially Aristada net sales grew 6% compared to the third quarter 2019, driven by 11% unit growth and again, partially offset by higher gross to net adjustments.

Underlying total prescription data for aerostar have demonstrated solid growth of 40% year over year in terms of months of therapy.

In December 2019, aerostat as market share for new prescriptions in terms of wants to therapy was 32% in the long acting or peppers, all market and 9% in the overall market for long acting atypical antipsychotics.

For the full year 2019, Aristada net sales increased 28% year over year to $189.1 million driven by volume growth.

Jim: For the full year 2019, Aristata Net Sales increased 28% year-over-year to $189.1 million, driven by volume. Gross net adjustments were 49% for the year compared to 44.3% in the full year 2018. Moving on to our Manufacturing and Royalty business, in the fourth quarter, our Manufacturing and Royalty revenues were $107.3 million, compared to $167.4 million in the same period in 2018. For the full year, we recorded manufacturing and royalty revenues of $447.9 million, compared to $526.7 million in the prior year. This decrease reflects a decline in revenues from the Ampera-Fampera franchise.

Gross to net adjustments were 49% for the year compared to 44.3% in the full year 2018.

Moving onto our manufacturing royalty business in the fourth quarter, our manufacturing royalty revenues were $107.3 million compared to $167.4 million in the same period in 2018.

For the full year, we recorded manufacturing and royalty revenues of $447.9 million compared to $526.7 million in the prior year.

This decrease reflects a decline in revenues from the empiric Sampere Refranchise following generic competition to ampyra entering the market in the United States in 2018.

Jim: Following generic competition for Ampera entering the market in the United States in 2018, as well as a one-time payment of $26.7 million from Zeeland Pharma that was recognized in the fourth quarter of 2018. 2019 revenues from Risperdal-Consta, Invegas-Estena, and Invega-Trinza increased 3% compared to 2018 to $323.3 million, as increased end market sales of Invegas Asthena and Invega Trinza were largely offset by fewer manufacturing batches and lower end market sales for Risperdal Concepts, and by the loss of the Invegas Astena 1.5% patent royalty In 2019, we recorded R&D revenues of $11.1 million for the fourth quarter and $52.8 million for the full year, primarily driven by the reimbursement of development expenses for Vumerity related to our collaboration with Buying. Following FDA approval of Vumerity in the fourth quarter, we received a $150 million milestone, of which $144.8 million was recorded as license revenue and $5.2 million as R&D revenue. We receive a 15% royalty on net sales of Umeri, and this royalty has the potential to be an important financial contributor for us.

As well as a onetime payment of $26.7 million from Zealand pharma that was recognized in the fourth quarter of 2018.

2019 revenues from Risperdal, Consta, Invega, Sustenna and as big a trinza increased 3% compared to 29 to 2018 excuse me to $323.3 million.

As increased end market sales of Invega, Sustenna and Invega trinza were largely offset by fewer manufacturing batches and lower end market sales for Risperdal consta and by the loss of the Invega Sustenna, 1.5% patent royalty in the United States as of May 2019.

In 2019, we recorded R&D revenues of $11.1 million for the fourth quarter and $52.8 million for the full year, primarily driven by the reimbursement of development expenses for remarried related to our collaboration with Biogen.

Following FDA approval of America in the fourth quarter, we received a $150 million milestone payment of which $144.8 million was recorded as license revenue and $5.2 million as R&D revenue.

We receive a 15% royalty on net sales of remarried and this royalty has the potential to be an important financial contributor for us.

In terms of expenses, our total operating expenses for 2019 were inline with our expectations.

Jim: In terms of expenses, our total operating expenses for 2019 were in line with our expectations. Our R&D expenses for 2019 were $512.8 million, compared to $425.4 million for the prior year. The year-over-year increase was primarily due to our acquisition of Rodin in the fourth quarter, which included an upfront cash payment of $98.1 million. This transaction was accounted for as an asset acquisition, and $86.6 million of this upfront payment was determined to be in-process R&D and consequently recorded as R&D expense in Q4. If you exclude this R&D expense relating to the acquisition of Rodin, R&D expenses of $111.6 million in Q4 were relatively flat compared to Q4 of last year. SG&A expenses for 2019 were $599.4 million compared to $526.4 million for the prior year. Reflecting investments in our commercial organization in support of both Aristotle and Vivica.

R&D expenses for 2019 were $512.8 million compared to $425.4 million for the prior year.

The year over year increase was primarily due to our acquisition of Rodin in the fourth quarter, which included an upfront cash payment of $98.1 million.

This transaction was accounted for as an asset acquisition and $86.6 million of this upfront payment was determined to be in process R&D and consequently recorded as R&D expense in Q4.

If you exclude this R&D expense related to the acquisition of Rhoda R&D expenses of $111.6 million in Q4 were relatively flat compared to Q4 last year.

SGN expenses for 2019 were $599.4 million compared to $526.4 million for the prior year, reflecting investments in our commercial organization in support of both Aerostar and Vivitrol.

Jim: Turning to our balance sheet, we ended 2019 with approximately $614 million in cash and total investment, compared to approximately $620 million at the end of 2018. The company's total debt outstanding was approximately $277 million at the end of 2019. Let me now shift to our financial expectations for 2020, which reflect activities we have undertaken to position Alkermes for long-term growth and profitability. Our full financial expectations are outlined in the press release we issued earlier this year. For the top line, we expect total revenues to be in the range of $1.03 to $1.08 billion, which includes expectations for continued growth of Vivitrol and Aristide. For Vivitrol, we expect net sales to be in the range of $340 to $355 million, and gross to net adjustments of approximately 50%.

Turning our balance sheet, we ended 2019 with approximately $614 million in cash and total investments compared to approximately $620 million at the end of 2018.

The company's total debt outstanding was approximately $277 million at the end of 2019.

Let me now shift to our financial expectations for 2020, which reflect activities. We have undertaken the position alkermes for long term growth and profitability.

Our full financial expectations are outlined in the press release, we issued earlier this morning.

For the topline we expect total revenues to be in the range of $1.03 billion to $1.08 billion, which includes expectations for continued growth of Vivitrol and aristada.

For Vivitrol, we expect net sales to be in the range of $340 million to $355 million.

And gross to net adjustments of approximately 50%.

Jim: Due to the consolidation of certain Medicaid plans into broader buying consortiums that we expect will increase the supplemental discounts in certain states going forward. For Aristotle, we expect net sales in the range of $220 to $235 million, reflecting approximately 20% year-over-year growth to the midpoint. Despite expected gross to net adjustments increasing to approximately 52 percent due to similar consolidation of certain Medicaid plans and anticipated increased volume through the VF.

Due to the consolidation of certain Medicaid plans into Brian broader buying consortiums that we expect will increase the supplemental discounts in certain states going forward.

For Aerostar do we expect net sales in the range of $220 million to $235 million.

Reflecting approximately 20% year over year growth to the midpoint.

Despite expected gross to net adjustments increasing to approximately 52%.

Due to similar consolidation certain Medicaid plans and anticipated increased volume through the VA.

In line with historical seasonal patterns due to the impact of yearend inventory build and the reset of commercial plan deductibles. We expect our first quarter 2020, net sales would be down sequentially for both vivitrol and aristada with growth expected to resume in the second quarter.

Jim: In line with historical seasonal patterns due to the impact of year-on-inventory build and the reset of commercial plan deductibles, we expect our first quarter 2020 net sales to be down sequentially for both Vivitrol and Aristata, with growth expected to resume in the second. It's important to note that our 2019 topline results included approximately $200 million of license and R&D revenues from Biogen related to the development and approval of Vermerity. For comparative purposes, our 2020 revenue expectations reflect top-line growth of just over 8% year-over-year when excluding those Biogen contributions to our 2019 revenue. In terms of our operating expenses, as we evaluated our cost structure last year, we implemented a restructuring designed to deliver savings of approximately $150 million in 2020, with about one-third related to R&D and two-thirds driven by SG&S, while preserving our ability to invest appropriately in what we believe to be our highest value opportunity. The $150 million in planned savings was measured against our pre-restructuring 2020 internal budget, which aligns with the September 2019 sell side consensus for our 2020 expenses. We subsequently adjusted this number by $20 million following the acquisition of Rodin to account for anticipated incremental R&D spending. The financial expectations that we're providing today reflect our expected achievement of these savings.

It's important to note that our 2019 topline results included approximately $200 million of license in R&D revenues from Biogen related to the development and approval of were Meredith.

For comparative purposes, our 2020 revenue expectations reflect topline growth of just over 8% year over year, when excluding those biogen contributions to our 2019 results.

In terms of our operating expenses as we evaluated our cost structure last year, we implemented a restructuring designed to deliver savings of approximately $150 million in 2020.

With about one third related R&D and two thirds driven by SGN.

While preserving our ability to invest appropriately and what we believed to be our highest value opportunities.

The $150 million in plan savings was measured against our pre restructuring twentytwenty internal budget, which aligned with the September 2019 sell side consensus for our 2020 expenses.

We subsequently adjusted this number by $20 million following the acquisition of Rhoda to account for anticipated incremental R&D spend.

The financial expectations that we're providing today reflect our expected achievement of these savings.

R&D expenses are expected to be in the range of $405 million to $430 million, reflecting the impact the predicted impact of the restructuring an incremental investments in the H. JAK inhibitor platform that we acquired from Rodin.

Jim: R&D expenses are expected to be in the range of $405 to $430 million, reflecting the predicted impact of the restructuring and incremental investments in the HDAC inhibitor platform that we acquired from Rodan. Included in this overall R&D expense are expected investments in advancing the ALCS 4230 Clinical Development Program and Lifecycle Management Initiatives for our commercial products and ALCS 3831, and Investments in our Preclinical Portfolio, including the HDAC Inhibitor Platform. Our R&D expenses also include investments in our medical affairs efforts and manufacturing operations, both in support of our commercial products and pipeline. SG&A expenses are expected to decrease to be in the range of $535 million to $560 million in 2020, also reflecting the impact of our restructuring. Estimated investment in SG&A is primarily related to the complex infrastructure needed to commercialize our proprietary products in addiction and schizophrenia, as well as investments in pre-launch activities for ALCS 3831.

Included in this overall R&D expense, our expected investments in advancing the out 40, 230 clinical development program and lifecycle management initiatives for our commercial products and Alex three Athree one.

And investments in our preclinical portfolio, including the H. deck inhibitor platform.

R&D expenses also include investment in our medical affairs efforts and manufacturing operations, both in support of our commercial products and pipeline candidates.

As she in expenses are expected to decrease to be in the range of $535 million to $560 million in 2020 also reflecting the impact of our restructuring.

Expected investment in SGN is primarily related to the complex infrastructure needed to commercialize our proprietary products. In addition in schizophrenia.

As well as investments in prelaunch activities for Alcs, three or three one.

Within assign PDUFA target action date in November 2020, and assuming a 90 day D.A. scheduling period.

Jim: With an assigned PDUFA target action date in November 2020, and assuming a 90-day DEA scheduling period, the majority of investments in the expansion of our sales organization in support of Alex 3831 would not occur until early 2021. We expect 2020 GAAP net loss to be in the range of $130 to $160 million and non-GAAP net income to be in the range of $40 million to $70 million. Excluding the $150 million milestone payment that we received from Biogen in 2019, our expectations for non-GAAP net income in 2020 reflect a year-over-year increase of approximately $90 million to the midpoint of our 2020 guidance. We enter 2020 in a position of financial strength and look forward to advancing our development pipeline candidates in both neuroscience and oncology, growing our commercial portfolio, and further leveraging our P&L to drive sustained non-gap profitability.

The majority of investments in the expansion of our sales organization and supportive Alex three Athree, one would not occur until early 2021.

We expect 2020, GAAP net loss to be in the range of $130 million to $160 million and non-GAAP net income to be in the range of 40 million to $70 million.

Excluding the $150 million milestone payment that we received from Biogen in 2019, our expectations for non-GAAP net income in 2020 reflect a year over year increase of approximately $90 million to the midpoint of our 2020 guidance range.

We entered 2020 in a position of financial strength and look forward to advancing our development pipeline candidates in both neuroscience in oncology growing our commercial portfolio and further leveraging our personnel to drive sustained non-GAAP profitability.

With that I'll turn the call over to Richard that's great. Thank you, Jim and good morning, everyone. So weve built a billion dollar topline business through developing important medicines 2019 was highlighted by important operational achievements across the portfolio with the approval of humanity for multiple sclerosis. The submission of the Alcs 30 31 in da.

Richard F. Pops: I will turn the call over to Richard. 2019 was highlighted by important operational achievements across the portfolio, with the approval of VUMERITY for multiple sclerosis, the submission of the ALKS3831 NDA, the presentation of initial efficacy and safety data from our ALKS4230 clinical program, and important positive phase 3 data from the ARISTA Alpine study and the VUMERITY Evolve MS2 study. In 2019, we also focused on actively shaping the future of the business through a rigorous assessment of our products, our pipeline, and our structure, and took important steps to position the company for long-term growth. We implemented a strategic restructuring in order to reduce our cost structure and, in so doing, accelerate and drive sustained non-gap profitability.

The presentation of initial efficacy and safety data from our Alcs 40, 230 clinical program and important positive phase three data from the Arista Alpine study and the humidity evolve Emmis to study.

In 2019.

We also focused on actively shaping the future of the business through a rigorous assessment of our products our pipeline and our structure and took important steps to position the company for long term growth.

We implemented a strategic restructuring in order to reduce our cost structure and in so doing accelerate and drive sustained non-GAAP profitability.

Richard F. Pops: We acquired Rodan Therapeutics, building on our experience in CNS diseases and expanding our development efforts into a wide range of neurodegenerative disorders. And we strengthened our board through two new independent directors, one a former public company CFO focused on value creation, and the other an oncology thought leader and a. As we enter 2020, our key priorities are clear. Drive the growth of Vivitrol and Aristata through commercial execution. Prepare for the launch of ALKS3831 in Schizophrenia and Bipolar I Disorder. Advance the development of ALKS4230 in oncology and build out our HDAC inhibitor platform. So I'll take these briefly in turn.

We acquired Rodin Therapeutics building on our experience in CNS diseases, and expanding our development efforts into a wide range of Neurodegenerative disorders, and we strengthened our board through two new independent directors want to form Republic company CFO focused on value creation and the other an oncology thought leader in expert.

So as we enter 2020.

Key priorities are clear drive the growth of Vivitrol and aristada through commercial execution.

Prepare for the launch about 30 31 in schizophrenia and bipolar one disorder.

And the development of Elks 40, 230 in oncology and build out our h. deck inhibitor put platform.

We'll take these briefly in turn.

Our work in addiction and in schizophrenia with ARISTOTLE exemplifies many of the core values of this company.

Richard F. Pops: Our work in addiction and in schizophrenia with Aristotle exemplifies many of the core values of this company. We're out there every day through our science, our medicines, and our advocacy working to advance patient-centered care for people with these serious conditions. We are making a real world impact, and we're very proud of it. Alkermes is a positive force for change, and these medicines are incredibly important elements of our business. Vivitrol is helping to address the public health crisis represented by opioid dependence.

We're out there every day through our science, our medicines and our advocacy working to advance patient centered care for people with these serious conditions, we are making a real world impacting we're very proud of it alkermes is a positive force for change and these medicines are incredibly important elements of our business.

Vivitrol is helping to address the public health crisis represented by opioid dependence.

Richard F. Pops: It's unlike any other pharmaceutical product, from the infrastructure required to foster adoption to its geographically driven growth, which is reliant in large part on state policy and funding. We've invested many years into understanding this land and the Treatment Paradigm in order to increase access and drive awareness for vivitrol. Its growth trajectory is dynamic and challenging to predict. In 2020, we'll continue to focus on driving growth and profitability and extending the impact of this method. Aristotle demonstrated solid year-over-year growth in 2019.

It's unlike any other pharmaceutical products from the infrastructure required to foster adoption to it's geographically driven growth, which is reliant in large part on state policy in funding.

We've invested many years into understanding this landscape.

The treatment paradigm in order to increase access and drive awareness for Vivitrol.

Its growth trajectory is dynamic and challenging to predict in 2020, we'll continue to focus on driving growth and profitability and extending the impact of this medicine.

ARISTOTLE demonstrated solid year over year growth in 2019, 2020 is about execution with a differentiated product family a strong payer access profile and a compelling value proposition, we have a clear opportunity to growth group to drive the growth Aerostar.

Richard F. Pops: 2020 is about execution. With a differentiated product family, a strong pair access profile, and a compelling value proposition, we have a clear opportunity to drive the growth of Aristotle in 2020. These two products are growing and comprise an increasing percentage of our revenue, and this revenue engine continues to evolve. In 2020, we expect a new stream of royalty revenues from Vumerity, a novel, next-generation oral fumarate for the treatment of relapsing forms of MS, which was discovered and developed by Alkermes and which received FDA approval last quarter. Iogen is launching Vumerity into a large and dynamic U.S. market for MS. And last week, Techfedera's IPR decision was a positive development for this market. We receive a 15% royalty on net sales of Vumerity.

In 2020.

These two products are growing and comprise an increasing percentage of our revenue and this revenue engine continues to evolve in 2020, we expect a new stream of royalty revenues from drew Mary and novel next generation oral fumarate for the treatment of relapsing forms of Emmis, which was discovered and developed by alkermes, and which received FDA approval last quarter.

Biogen is launching be merit into a large and dynamic us market for CMS and last week last week texture. There as IP. Our decision was a positive development for this market.

We receive a 15% royalty on net sales of new meriting. This product has been profitable for us from the first units sold so were often running and we're looking forward attracting the progress of Biogens launch.

Richard F. Pops: This product has been profitable for us from the first unit sold, so we're off and running, and we're looking forward to tracking the progress of Biogen's launch. The acceptance of the ALCS3831 NDA for Schizophrenia and Bipolar I Disorder last month was an important milestone in this program. We're planning for potential approval of 3831 at the end of the year, which would contribute to and grow our psychiatric franchise. The investments we've made in our Aristotle Commercial Organization provide a strong platform for the launch of 3831, and we are well positioned to leverage our established presence with physicians, thought leaders, payers, and policy makers in psychiatry. Across schizophrenia and bipolar 1 disorder, efficacy is key to successful outcomes. With the efficacy of olanzapine and a differentiated tolerability profile, 3831 has the potential to be an important new treatment option. We look forward to working with the agency through its review of the NDA and updating you on the preparations for launch. Our pre-launch work is focused on two areas, disease state education and engagement with a range of payers. So I'll turn to the development pipeline.

The acceptance of the X 30, 31, India for schizophrenia, and bipolar one disorder last month was an important milestone in this program.

We're planning for potential approval of 30 at 31 at the end of the year, which would contribute to and grow our psychiatry franchise.

The investments we've made in our ARISTOTLE commercial organization provide a strong platform for the launch of 30 31, and we are well positioned to leverage our established presence with physicians thought leaders Payors and Pal policymakers in psychiatry space.

Across schizophrenia, and bipolar when disorder efficacy is key to successful outcomes with the efficacy of Elanzapine in a differentiated tolerability profile 30, 31 has the potential to beat important new treatment option.

We look forward to working with the agency through its review of the NDA in updating you on the prepared on the preparations for launch our pre launch work is focused in two areas disease state education and engagement with a range of payers.

So I'll turn to the development pipeline.

Richard F. Pops: 4230 is our investigational, engineered IL-2 fusion protein designed to selectively expand tumor-killing immune cells while avoiding the IL-2-induced activation of immunosuppressive cells. Harnessing the anti-tumor activity of the IL-2 pathway continues to be one of the most exciting opportunities in immunoecology. The 4230 Clinical Development Program has two core elements: Artistry 1, our intravenous dosing study, and Artistry 2, our subcutaneous dosing study. In 2019, we made important progress in both and presented initial efficacy and safety data from Artistry 1 at CITSE last November. The Artistry 1 data have continued to emerge since that presentation. As of a December 23rd data cut, we'd observed new partial responses in both PEMBRO-approved and unapproved tumor types, and a safety profile consistent with what we presented at SIDS.

40, 230 is our investigational engineered aisle to fusion protein designed to selectively expand tumor killing immune cells, while avoiding the aisle to induced activation of immunosuppressive cells.

Harnessing the anti tumor activity the aisle to pathway continues to be one of the most exciting opportunities in immuno oncology.

The 40 230 clinical development program has two core elements artistry, one our intravenous dosing study in artistry to our subcutaneous dosing study.

In 2019, we made important progress in both and presented initial efficacy and safety data from artistry one at city last November.

The artistry one data have continued to emerge since that presentation as of December 23rd data cut we observed new partial responses in both Pembro approved and unapproved tumor types and a safety profile consistent with what we presented at Citi.

As of February 11, both patients with partial responses that we reported on it 50 had been on therapy for more than a year and will discuss these results and others in more detail at future medical meetings.

Notably 40 230 of the only aisle to variant program in active clinical development with potential for subcutaneous dosing.

Richard F. Pops: As of February 11th, both patients with partial responses that we reported on at CITSE had been on therapy for more than a year, and we'll discuss these results and others in more detail at future medical meetings. Notably, 4230 is the only IL-2 variant program in active clinical development with the potential for subcutaneous doses. We're particularly encouraged by the initial data emerging from Artistry 2, and today I'll give you a brief overview of some of the initial findings from that study. In the initial escalation cohorts of Artistry 2, examining weekly and once every three-week dosing, the subcutaneous administration of 4230 showed a pharmacokinetic profile that was consistent with our prediction. The initial escalation doses also demonstrated biological activity as measured by the expansion of effector cells.

We're particularly encouraged by the initial data emerging from artistry too and today I'll give you a brief overview of some of the initial findings from that study.

In the initial escalation cohorts of artistry to examining weekly and once every three week dosing. The subcutaneous administration and 40 230 showed a pharmacokinetic profile that was consistent with our predictions.

The initial escalation doses also demonstrated biological activity as measured by expansion of the effector cells.

The emerging data observed thus far in artistry to suggest that both the weekly and once every three weeks subcutaneous regimens may have potential for improved tolerability profile as compared to the IB dosing regimen.

As of December 19th data cut there were no reports of serious adverse adverse events related to study drug or discontinuations due to adverse events in the Subcu study.

Richard F. Pops: The emerging data observed thus far in ARTISTRY 2 suggests that both the weekly and once every three weeks subcutaneous regimens may have potential for an improved tolerability profile as compared to the IB dosing regimen. As of a December 19th data cut, there were no reports of serious adverse events related to study drug or discontinuations due to adverse events in the sub-Q study. In the ongoing dose escalation phase of Artistry 2, 11 of 19 patients that were dosed with the 4230 regimen continue on treatment as of February 11th, with 5 of those subjects having received 6 months of treatment or more. In terms of efficacy, Artistry 2 is designed to provide a number of interesting data sets. Patients enrolled have rapidly progressing disease, and the six-week monotherapy lead-in period has the potential to help demonstrate single-agent activity of 4230. As of the December data cut, nine of 11 patients with a first scan had stable disease, and a majority of these nine patients continued to have stable disease upon their second scan.

In the ongoing dose escalation phase of our street to 11 of 19 patients that were dosed with the 40 230 regimen continue on treatment as of February 11th with five of those subjects, having received six months of treatment or more.

In terms of efficacy artistry two is designed to provide a number of interesting datasets.

Patients enrolled have rapidly progressing disease and the six week monotherapy elite in period has the potential to help demonstrate single agent activity of 40 230.

As of the December Datacom nine of 11 patients with the first scan had stable disease and a majority of these nine patients continue to have stable disease upon their second scan.

As we expand the clinical development program were significantly expanding our clinical trial network outside of the us and we're in the process of opening new sites to accelerate enrollment we expect the first of these sites to open for enrollment later this quarter.

From a strategic perspective with increased visibility into the potential to subcutaneous dosing regimen, and Alex 42 thirds emerging efficacy profile, we're positioned now to evaluate opportunities for strategic collaboration in 2020.

Richard F. Pops: As we expand the clinical development program, we're significantly expanding our clinical trial network outside of the U.S., and we're in the process of opening new sites for accelerated enrollment. We expect the first of these sites to open for enrollment later this quarter. From a strategic perspective, with increased visibility into the potential of the subcutaneous dosing regimen and ALKS4230's emerging efficacy profile. We are positioned now to evaluate opportunities for strategic collaboration in 2020.

With the potential to be complimentary with a variety of cancer treatment approaches collaboration will be key to exploring and maximizing the potential with 40 230 as a treatment option.

Next I'll now turn to our H. JAK inhibitor platform.

The Rodin transaction builds on our broad experience in psychiatry and allows us to explore a wide array of neuro psychiatric diseases that are characterized by synaptic loss in dysfunction, such as schizophrenia, and depression as well of neuro as neurodegenerative diseases, like all timers, and Huntingtons and other developmental disorders.

Richard F. Pops: With the potential to be complementary to a variety of cancer treatment approaches, collaboration will be key to exploring and maximizing the potential of 4230 as a treatment option. Next, I'm going to turn to our HDAC inhibitor class. The Rodin Transaction builds on our broad experience in psychiatry and allows us to explore a wide array of neuropsychiatric diseases that are characterized by synaptic loss and dysfunction, such as schizophrenia and depression, as well as neurodegenerative diseases like Alzheimer's and Huntington's, and other developmental disorders. HDAC inhibitors are powerful epigenetic regulators that have the potential to drive the formation of new synapses in the brain and HDAC inhibitors have been approved for oncology. However, these agents are limited by hematologic toxicities, and it was never clear whether these toxicities could be separated from their pro-synaptic effects. HDAC's function is in association with specific multi-protein complexes.

Each JAK inhibitors are powerful epigenetic regulators that have the potential to drive formation of new snaps is in the brain and by doing so address some of the most disruptive clinical symptoms that accompany nearer to do to Neurodegenerative diseases.

H. deck inhibitors hibbett approved doesn't quality agents.

However, these agents are limited by hematologic toxicities and it was never clear whether these toxicities could be separated from their pro synaptic effects.

Each decks function in association with specific multi protein complexes.

Our chemistry targets. These specific subsets, one of which is called co rest, which is directly involved in repression of posted attic genes in neurons.

This program is advancing with preclinical research and India, enabling activities with the primary focus on H. that co rest inhibitors for Cnf top of fees.

Richard F. Pops: Our chemistry targets these specific subsets, one of which is called co-rest, which is directly involved in the repression of pro-synaptic genes in neurons. This program is progressing with pre-clinical research and IND-enabling activities with a primary focus on HDAC co-risk inhibitors for synaptopathy. Anticipating our move into the clinic, we're developing biomarkers and translational tools to give us early insight into clinical development. We are very excited about the biology and the chemistry around this platform. This investment is reflective of our longstanding commitment to bring new and innovative therapeutic options to patients living with chronic CNS diseases where the unmet medical need is high. So I'll end there. Our strategy and path to driving value creation for shareholders is clear. We have a billion-dollar top line with growing proprietary commercial products, a commitment to sustain non-gap profitability, and an exciting pipeline in neuroscience and oncology. 2020 will be an important year across the portfolio, and we'll look forward to updating you on our progress. So with that, I'll turn it back to Sandy to run the Q&A.

Anticipating our move into the clinic, we're developing biomarkers and translational tools to give us early insight into clinical development.

We're very excited about the biology and the chemistry around this platform. This investment is reflective of our longstanding commitment to bring new and innovative therapeutic options to patients living with chronic CNS diseases, where the unmet medical need is high.

So while in there our strategy and path to driving value creation for shareholders is clear we have a $1 billion topline with growing proprietary commercial products a commitment to sustain non-GAAP profitability and an exciting pipeline in neuroscience and oncology 2020 will be an important year across the portfolio and we'll look forward to update.

You on our progress so with that I'll turn it back to sandy to run acuity.

Great. Thank you Richard Rob will now open the call for Q and AG.

Thank you Sandy at this time will be conducted question and answer session. If you like to ask your question. Please press star one on your telephone keypad and the confirmation total indicate your line is in the question Q.

You May press star to if you'd like to move your questions from the Q.

Participants using secure equipment, maybe necessary to pick up your handset before pressing the star Keith.

Developing so we pull for questions.

Sandra Coombs: Great. Thank you, Richard. Rob, we'll now open the call for Q&A. Thank you, Sandy.

Thank you and our first question is from the line of Jason Gerberry with Bank of America.

unknown: At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.

Please proceed with your question.

Hey, good morning, Thanks for taking my question.

Just first question for me I wanted to follow up on your comment about exploring collaboration for four to 300 2020. So.

Is it fair to say that everything's on the table in terms of its such deals you're looking at are you looking at.

Collaborations where perhaps you can.

Jason Matthew Gerberry: One moment, please, while we poll for questions. Thank you, and our first question is from the line of Jason Gerberry with Bank of America. Please proceed with your question. Hey, good morning, and thanks for taking my question. Rich, just the first question for me: I wanted to follow up on your comment about exploring collaboration for 4230 in 2020. So, is it fair to say that, you know, everything's on the table in terms of the types of deals you're looking at, or are you looking at collaborations where perhaps you can partner with companies to help co-fund R&D to explore more combinations with 4230 in different tumor settings? And then my second question, just the guide on Vivitrol looks like it implies about a low single-digit drag on net pricing. Just sort of curious if you'd characterize that as the trend we should be modeling for Vivitrol on a go-forward basis, that effectively net pricing is kind of down low single digits. Thanks.

Partner with companies to help co fund R&D to explore more combinations with for two to REO and different tumor settings, and then my second question just.

The guide on Vivitrol looks like it implies about a low single digit drag on net pricing just sort of curious if you'd characterize that as the trend we should be modeling for vivitrol on a go forward basis that effectively net pricing is kind of down low single digits. Thanks.

Mortgages and I'll take the first I'll have Jim and take the second one so yes, I think it's fair to say conceptually everything's on the table as we look at a 40 230 collaboration.

The caveat being the objective is is to maximize the expected net present value of the whole program and thats going to be done by increasing the number of.

Richard F. Pops: I'll take the first one, and I'll have Jim and Iain take the second one. So, yeah, I think it's fair to say conceptually everything's on the table as we look at a 42-30 collaboration. The caveat being, the objective is to maximize the expected net present value of the whole program, and that's going to be done by increasing the number of tumor types and lines of therapy that we can explore. What's interesting is that already, as the program is progressing, we're being approached to look at all kinds of different combinations, from IO-IO combinations to targeted cancer therapies, radiotherapy, conventional chemotherapies, and the like. Because you can see why this IL-2 pathway being activated selectively as we're doing it would just conceptually be a reasonable complement to a number of different applications. So the value of the program will be maximized by the scope of the clinical program that we have to support. By ourselves, we couldn't come close to funding all the different operations.

Tumor types and lines of therapy. The we can explore what's interesting is that already as it has the program is progressing we're being approached to look at all kinds of different combinations from Io Io combinations to targeted cancer therapies radiotherapy conventional chemotherapy use and the like because you can.

See why.

This I'll to pathway the activated selectively as we're doing it would just conceptually be reasonable complement to a number of different applications. So that the value of the program will be maximize by by the scope of the clinical program that we have displayed by ourselves we could we couldn't come close to funding all the different opportunities and we've been waiting to.

Do that until we had enough information to say, okay. We truly have an agent here that is meeting the profile that we designed is to have and I'm not ready to say, we're completely there yet but all the indications are going that direction I think during this year that dataset should mature to the point. So I don't know, whether we'll whether we would consummate a collaboration twentytwenty.

Richard F. Pops: And we've been waiting to do that until we had enough information to say, okay, we truly have an agent here that is meeting the profile that we designed it to have. And I'm not ready to say we're completely there yet, but all the indications are going that direction. I think during this year, that data set should mature to the point where I don't know whether we will consummate a collaboration in 2020. We don't need to. It's not really limiting at this point. We have the funding and the capacity to do it. But I think over the course of this year, the data set is going to be sufficiently complete to get a good sense of what this molecule can become.

We don't need to too it's not read limiting at this point, we have the funding in the in the and the capacity to do it but I think over the course of this year. The dataset is going to be sufficiently.

Complete well to get get a good sense of what this month MEP molecule can can become.

And Jason on the pricing I mean, I think you picked up on onto competing trends that are happening with Vivitrol. You know as we typically do we take our volume growth and extrapolate that forward because it's so hard to predict the changes that happened on a state by state level and this year, we are predicting a change by a few percentage points in gross to nets last year around 40.

Jim: And Jason, on pricing, I mean, I think you picked up on two competing trends that are happening with Vivitrol. You know, as we typically do, we take our volume growth and extrapolate that forward because it's so hard to predict the changes that happen on a state-by-state level. And this year we are predicting a change by a few percentage points in growth to net. Last year we were around 48%. We're predicting next year to be 50%. Again, that's largely driven by where the state business comes from because every state has a different Medicaid program. And so I would say that's really a course of adjustment that we see today. We're not yet ready to see that continuing in the future.

8% were predicting next year to be 50%.

Again, thats largely driven on where the state business comes from because every state has a different Medicaid program and so I would say that's really a course of adjustment that we see today, we're not yet ready to see that that continuing out in the future and again a lot will depend on where we see the growth coming.

In the future from various states.

The last thing I'd say is we're working really hard into 2020 to focus on the alcohol indication for Vivitrol, which is a part of the payer mix that has more commercial payment as opposed to opiates and so we're working hard there to see if we can counteract that pressure on pricing that we're going to see in 2020.

Jim: And again, a lot will depend on where we see growth coming from in the future from various states. You know, the last thing I'd say is we're working really hard into 2020 to focus on the alcohol indication for Vivitrol, which is a part of the payer mix that has more commercial payment as opposed to opiates. And so we're working hard there to see if we can counteract that pressure on pricing that we're going to see in 2020. Great, and if I could just follow up.

Great and if I could just follow up is there any impact to the warning letter on vivitrol baked in the guidance.

No I think I think our guidance was was developed just.

Normal course.

Okay. Thank you.

Thanks, Jason.

Our next question from the line of Chris Shibutani with Cowen and company. Please proceed with your question.

Jim: And if I could just follow up, is there any impact to the warning letter on Vivitrol baked into the guidance?

Hi, everyone. This is Tim Barrett, Chris as a couple of questions. The first one is.

Jim: No, I think our guidance was developed just in our normal course.

Jim: Thank you. Thanks, Jason. Our next question is from the line of Chris Shibutani with Cowan & Company. Please proceed with your question. Hi everyone, this is Pam Barrett on behalf of Chris.

Looking forward to the next one to three years and the expenses R&D and DNA what percentage.

Chris Shibutani: I have a couple of questions. The first one is looking forward to the next one to three years and the expenses, R&D, and SG&A. What percentage of those do you think would be dedicated to oncology now that you've said you may partner, but that's not for certain?

So you think would be dedicated to oncology now that you know you said you you may partner, but.

Well I think a lot will depend Pam on on the exact partnership come in as rich outline theres, both commercial as well as scientific.

Jim: Well, I think a lot will depend, Pam, on the exact partnership. I mean, as Rich outlined, there's both commercial as well as scientific.

Logic to partnering 40, 230, and I and.

Jim: Logic to partnering 4230. And I think if we, you know, in the broadest sense the way I think about it, if we have a partner, we can probably attack a lot more potential indications and spend a lot of money together with a partner. If Alkermes is pursuing it individually, we'll certainly target that. And the broadest guidance I can give you so far for beyond 2020 is that we're committed to our profitability. And so our investment in R&D across our portfolio will be made with that discipline in mind.

I think.

If we.

The broader sense the way I think about it if we are have a partner we can probably attack a lot more potential indications and spend a lot.

Money together with a partner if alkermes is pursuing it individually will certainly target that and the broader.

Guidance I can give you so far for beyond 2020 is that we're committed to our profitability and so our investment in R&D across our portfolio will be made with that discipline in mind.

Our next question is specifically about the regulatory path.

Richard F. Pops: Our next question is specifically about the regulatory path for 3831. First, for schizophrenia, and secondly, for bipolar disorder. Can you let us know how likely or not you think it would be that an ADCOM would be held, and why?

Great. Thanks, first for schizophrenia, and secondly for bipolar disorder.

Can you, let us know how likely or not you. Thank you would be that.

Tom would be held and why.

Yes, so rude recall that we file the NDA for both indications. So we expect if the drug has approved there will be improved approved for both indications and.

Richard F. Pops: Yeah, so recall that we filed the NDA for both indications. So we expect if the drug is approved, it will be approved for both indications. And we've taken to the logic of how we arrived at that agreement with FDA. When we received the notice of acceptance of the NDA last month, FDA indicated they had not made a decision yet on an adcom. We are preparing for an adcom because 3831 contains samidorphine, which is a new molecular entity. And by statute, typically FDA would think about taking that to an adcom. So we'll prepare for an adcom and see how their guidance evolves as they get further into the review.

We've we've taken to the logic.

How we arrived at that agreement with FDA. When we received the the notice of acceptance of the end da last month.

Ft indicated they not made a decision yet on an AD com, we're preparing for an AD com because 30 31 contain samidorphan, which is a new molecular entities and by statute and typically FD would we think about taking that to an outcome. So will prepare for an outcome.

And see what how their guidance evolves as they get further into the review.

Got you would anticipate providing investor update.

Richard F. Pops: Got it. And would you anticipate providing investors updates on whether the ad comms will be happening?

On the AD.

Well be happening.

Of course.

Richard F. Pops: Of course,

Well.

Umer Raffat: Thank you. The next question is from the line of Umer Raffat with Evercore. Please proceed with your question. Hi guys, thanks for taking my question. I had two, if I may.

Hi, Thanks, Tim.

Next question is from the line of Omar with Evercore. Please proceed with your questions.

Hi, guys. Thanks for taking my question I had two if I may 1st.

Umer Raffat: First, perhaps if I could clarify in brief, my understanding is there's a minimum Biogen will be giving you. I'm not super sure what that minimum is in terms of dollar or percent royalty, if you could clarify for us. It would be really helpful in modeling.

Perhaps if I could clarify and do Marty.

My understanding is there is a minimum biogen will be giving you.

Im not super sure what that minimum is on dollar percent royalty if you could clarify for us we really helpful in modeling.

Rachel: Secondly, on the R&D side, I noticed obviously there's a bit of an R&D increase year over year, and we also saw Lily Armel fail their randomized Cypress trials of lung cancer with pegylated IL-10. So, I guess my question is, how are you thinking about your R&D allocation to the IL-2 and IL-10 programs, and should we or should we not look into the randomized Cypress trials that Lily Armel conducted? Thank you very much.

Secondly, on R&D side, I noticed obviously, there's a bit of an R&D increase year over year.

And we also saw Lilly are more failed their randomize cypress trials of lung cancer with the Pegylated out and so I guess my question is.

How are you thinking about.

Your R&D allocation to the aisle to now 10 programs and should or should we not read into the randomized cypress trials that Lilly ARYMO conducted thank you very much.

Rachel: Thank you very much, Rachel. They're both good questions.

Hey words rates other both good questions at the very minimums are contractual minimums that we expect to be.

Richard F. Pops: The majority minimums or contractual minimums that we expect to be our modeling and Biogen's forecast for us would be exceeded by the 15% royalties, so they're probably not economically operational in 2020 or beyond. ,,, The Lilly failure absolutely affects our planning for IL-10. It was one thing in pancreatic cancer, but in small cell in combination with NEVO and PEMBRO, to strike out on both. So we are absolutely reassessing our decision to move forward into the clinic with our IL-10 construct. I'll go unaffected right, that's 4230 that's rolling, and so we're getting more and more positive momentum behind the 4230 Program for the reasons I outlined in my earlier remarks.

Our modeling and Biogens forecast for us would would be exceeded by the the 15% royalties. So they are probably not economically operational in 2020 or beyond.

[music].

The the Lilly failure, absolutely affects our planning for I'll turn it was one thing in pancreatic but in small cell in combination with Nivo and pembro to.

Strike out on both so we are absolutely reassessing our decision to move forward into the clinic with our oil 10 construct.

I will too on effective right. That's 40, 230, thats rolling and so.

We are getting more and more positive momentum between behind the 40 230.

Program for the reasons I outlined in my earlier remarks.

Thank you very much.

Corey Kazimoff: Thank you very much. Our next question is from the line of Corey Kazimoff with J.P. Morgan. Please proceed with your question. Hey guys, this is Mattheon on behalf of Corrie, and thanks for taking my questions. First one on LX4230, and based on the updated data you presented today, I'm just curious how you think about the weekly dose relative to the once-every-three-week regimen in terms of both PK and biological effect.

Our next question.

Our next question is from the line of Cory Kasimov with JP Morgan. Please proceed with your question.

Hey, guys Matthew on for Korean Thanks for taking my question first on Alex 40 230.

And based on the updated data presented today, just curious how you're thinking about the weekly dose relative to the once every three weeks regimen and terms about PK in biological effect.

Richard F. Pops: It's a great question, and we don't know the answer to it yet because we're still escalating in both. Both appear to have differentiated tolerability profiles. Both are driving biological responses, but it's too early to tell whether one is better than the other or whether they both might coexist. People have speculated about the idea of induction with weekly sessions and then maintenance every three weeks, but we just don't know yet. But we're quite excited to see these early returns.

It's a super question and we don't on the answer to it yet because we're still escalating in both.

Both appear to have differentiated tolerability profile, both are driving biological responses, but it's too early to tell whether whether one is better than the other or whether they both Michael good you can even people have speculated with the idea of induction with weekly and then maintenance on on every three weeks, but we just don't know yet, but we're quite excited to see.

These early returns.

Richard F. Pops: I got it. Thank you. And then, on to Emerity, is there a plan to submit regulatory filings outside the US? And if so, can you comment on potential timelines associated with this?

Got it. Thank you and then Mondrian Meredith as their plans at summit regulatory filings outside the U.S. and have so can you comment on potential timelines associated with that.

I think that questions best directed to Biogen.

Richard F. Pops: I think that question is best directed to Biogen.

Got it thanks for taking my question.

Richard F. Pops: That's about it. Thanks for taking my questions. You're welcome. Our next question is from the line of Brandon Folkes with Cantor Fitzgerald. Please proceed with your question. Hi, thanks for taking my questions. Firstly, could you just elaborate on your assumptions regarding the competitive environment for Vivitrol in opioid use disorder in 2020, as well as some of the sources of growth in that business, especially as we're seeing sublocade gain some traction. And then secondly, I know you touched on it, but could you just provide some additional insight into the alcohol use indication and whether you've seen growth there and sources of growth as well? Thank you.

Youre welcome. Thanks.

Our next question is from the line of Brandon Folkes with Cantor Fitzgerald. Please proceed with your questions.

Hi, Thanks for taking my questions. Firstly could you just elaborate on your assumptions regarding the competitive environment for Vivitrol in Nigeria to use disorder, and twentytwenty as well as some of the sources of growth in that business, especially as we're seeing some blockade.

Gain some traction and then shaky I know you touched on it but could you just provide some additional insight into the OCO, you syndication and whether you've seen gross fee and Tim sources of growth potential. Thank you.

Brandon Richard Folkes: I'll take it, Brandon. It's interesting.

I'll take a branded that it's interesting in opioid use disorder, and they're really only three medicines that are used for the treatment of opioid use disorder, and those be methadone and deepen orphan and vivitrol. The first two whether whether it be but often is used in the injectable form or in the sub lingual or tablet form.

Richard F. Pops: In opioid use disorder, there are really only three medicines that are used for the treatment of opioid use, those being methadone, buprenorphine, and Vivitrol. The first two, whether buprenorphine is used in the injectable form or in the sublingual or tablet form, these are both replacement medicines, and they're indicated for the maintenance treatment of opioid dependence. Whereas Vivitrol is indicated for prevention of relapse to opioid dependence following opioid detoxification. So they're really different medicines for different purposes, so I don't see any change necessarily conceptually in the positioning of Vivitrol in 2020 versus 2019 or 2018 or 2017. The principal impediment to the growth of Vivitrol in opioid use disorder is the fact that the treatment system has never really been oriented to the use of antagonist medicines.

It's.

These are both replacement medicines in their indicated for the maintenance treatment of opioid dependence, whereas vivitrol is indicated for prevention of relapsed opioid dependence following opioid detoxification.

So the really different medicines for different purposes. So I don't I don't see any change necessarily conceptually in the positioning of Vivitrol in 2020 versus 2019 or 20 802017, the principal impediment to growth of Vivitrol and opioid use disorder is the fact that the treatment system has never really been oriented to do some antagonism medis and tag.

This medicine, it's it was born and raised.

Richard F. Pops: It was born and raised in the opioid replacement philosophy, and we've been fighting that and building around it for the last several years, and we'll keep doing that. Alcohol is interesting because you may recall that the first approval for Vivitrol was for alcohol use. And it launched into an environment where medicines really weren't used at all.

In the opiate replacement.

Philosophy, and we've been fighting that in building around it for the last several years and we'll keep doing that alcohol is interesting because you may recall that the first approval for Vivitrol was four for alcohol use.

And it launched into into an environment, where medicines really weren't used at all and 12 step programs being the dominant form of treatment.

Richard F. Pops: Twelve-step programs being the dominant form of treatment. As Vivitrol has grown in opioid use disorder, now something on the order of 10,000 people will go on Vivitrol this week. You've had a much bigger halo or circle of physicians and treatment centers that are getting comfortable using Vivitrol. And there's been a virtuous cycle back to its use in alcohol as well. In alcohol, we really don't compete against buprenorphine or anything else. We compete against the lack of pharmacologic therapy at all.

As Vivitrol has grown in opioid use disorder now something on the order of 10000 people will go on Vivitrol. This week.

The you've had a much bigger halos or circle of physicians and treatment centers that are getting comfortable using vivitrol and theres been a virtuous cycle back to its use in alcohol as well.

How are we really don't compete against buprenorphine or anything else we compete against.

The lack of pharmacologic therapy at all.

Richard F. Pops: As Jim mentioned in his remarks, it's a different payer mix often in alcohol as well; it's a more commercial-oriented payer. So because we've had some growing traction... in alcohol in various states. We're going to shift some of our marketing resources more toward alcohol in 2020 and beyond, and we'll let you know how that goes. But we're excited about that, Jimmy, and I'm going to add to that.

As Jim mentioned in his remarks, it's a different payer mix often alcohol as well as more commercial oriented payer. So because we've had some growing traction.

In alcohol in various states, we're going to shift.

Some of our of our marketing resources more toward alcohol in 2020, and we think beyond and we'll we'll let you know how that goes but we're excited about that opportunity.

Jimmy and add to that no I think thats right and again so much of it depends on the state by state Ecoson in some states you see alcohol.

Jim: No, I think that's right. And again, so much of it depends on the state-by-state ecosystem. In some states, you see, alcohol is the place where we're starting to make inroads into growth. And I think, as Rich said, that offers a really nice growth opportunity for us in 2020, along with state and federal funding that's continuing to come from the opioid crisis. And we think Vivitrol should get its fair share of that as well. So that's where we're looking for growth in 2020. But since it's hard to predict how we're going, you know, each state will perform, we're going to maintain the tradition that we've had of guiding the current growth rates essentially into the next year.

[music].

Being the place where we're starting to make inroads in growth and I think as rich said that offers a really nice growth opportunity for us in 2020, along with state and federal funding Thats continuing to come from the opioid crisis, and we think Vivitrol should get its fair share that as well, so thats where were looking to growth in 2020, but since it's hard to predict how we're going.

Each state performs we've we're going to maintain the tradition that we've had of guiding to the current growth rates essentially into the next year.

Brandon Richard Folkes: Great. Thank you. Very helpful. Thank you. Our next question is from the line of Buren Amin with Jeffreys. Please proceed with your question. Yeah. Hi guys.

Great. Thank you very helpful.

Thank you. Our next question is from the line of parent amid with Jefferies. Please proceed with your question.

Hi, guys. Thanks for taking my questions.

Buren Amin: Thanks for taking my questions. Richard, on Aristata, I think you mentioned that you've captured 32% of NRXs in the LAI market. How is that split across institution channels versus community channels?

Richard on ARISTOTLE, I think you mentioned that you've captured 32% of spa and our taxes and the LPI market. How is that split across institution channels versus community channels and then on 40 230 in our Sri one I think you mentioned that use to prs extending out to beyond.

Richard F. Pops: And then on 4230 in Artistry 1, I think you mentioned that the two PRs are continuing out to beyond a year. Can you talk about the three stable disease patients and if they're continuing, if they've progressed, or if they've converted to responders? And then on Artistry 2, I guess, at CITSE, the company was evaluating the 0.6 milligram weekly dose and the 1 milligram Q3 weekly dose. So can you just talk about the NK and CD8 expansion and how that compared to the QD dosing regimen?

Year can you talk about the three stable disease patients and if they're continuing its a progress already converted to.

Responders.

And then and then on August three two I guess at sea.

The company was evaluating 0.6 milligram weekly dose and the one milligram Q3 weekly dose. So can you just talk about I guess and King CD eight.

Expansion and how that compared to the QD dosing regimen.

Yes, I won't be to answer all of those hearing and I'll look to Jim on the first one in terms of the split on the and our axis in channels. You know the answer then no we havent gone down to the level of detail and I'd say, it's pretty consistent across the institutional and community mental health centers I think the one place where we've talked about where our national share is.

Richard F. Pops: Yeah, I won't be able to answer all of those, Buren. I'll look to Jim on the first one, in terms of the split on the NRXs and channel. Do you know the answer to that one, Jim?

Jim: No, we haven't gone down to that level of detail. And I'd say it's pretty consistent across institutional and community mental health centers. I think the one place where we've talked about where our national share is below where we'd like to see it is in the VA. With the formulary acceptance earlier last year and then, you know, moving into the individual visions through the year, we think in 2020, we can start to get the VA penetration up to higher national numbers. And just to be clear, the 32% was in terms of months of therapy in the eripiprazole LAI market. We're at about 9% share in the overall atypical LAI market.

Below where we'd like to see it is in the VA.

With the formulary acceptance early last year, and then moving into the individual visions through the year. We think in 2020, we can start to get the VA penetration up to more national numbers and just to be clear the 32%.

Was in terms of months of therapy in the air Pip resolve LPI market worried about 9% share in the overall.

Atypical la market.

And on the are on the on the 40 230 stuff what I don't want to do is give anything more than we gave in the prepared remarks simply because.

Richard F. Pops: And on the 4230 stuff, what I don't want to do is give anything more than we gave in the prepared remarks, simply because we made a decision about some incremental data we put in on the call, but we still want to preserve the ability to present data at upcoming meetings. With respect to RSV-2, though, I will say, as we escalate Q weekly and Q3 weekly, we do think we'll be mimicking what we can achieve with high-dose IL-2, with so far looking like a tolerability profile that's different than what we've seen with IV. And there are some reasons for that that we'll explain at some later time, but we're quite excited about that. So those escalations continue in both of those dosing duration arms.

We've made a decision about some incremental data we've put in on the call, but but we still want to preserve the ability present data.

Coming meetings the.

With respect to there is three to though I will say.

As we escalate Q weekly in Q3 weekly we do think we'll be mimicking one can achieve.

With hydro sale to with so far looking like a tolerability profile of its that's different than what we've seen Ivy and there is some reasons for that they will explain at some later time, but we're we're quite excited about that so those escalations continue in both of those those those dosing duration arms.

Great. Thank you.

Richard F. Pops: Great. Thank you. You're welcome. Our next question comes from the line of Douglas Tsao with AC Wainwright. Hi, good morning.

You're welcome.

Our next question comes from the line of Douglas Tsao with HC Wainwright. Please proceed with your question.

Douglas Dylan Tsao: Thanks for taking the questions. Jim, maybe to start with, in terms of the guidance on the SG&A side, I think you indicated that most of the Salesforce buildout for 3831 will occur in the early part of 2021, just given scheduling. Just curious, are there going to be other pre-launch activities that we should account for when we think about the cadence of SG&A through the course of 2020? And then also curious about 3831, how much of a significant Salesforce addition we should expect and how much overlap between the script writing base you see between 3831 and Aristotle, or are they just really two different segments in terms of people who are writing LAIs versus patients who are writing something like 3831?

Hi, good morning, Thanks for taking the questions did.

Jim maybe to start on in terms of the guidance on the M&A side I think you indicated that most of the Salesforce build out for 30 831 will occur and in the early part of 2021, just given scheduling just curious are there going the other pre launch activity that we should account or when we think that cadence. So thats DNA through the course of 20.

20, and then just also curious on 30 to 31, how large how much of US significant. Salesforce addition, we should expect and how much overlap between the scrip writing based the between 30 and 31 and ARISTOTLE or are they just really two different segment to us in terms of people who are wide annualized versus.

Patients who are right in something like 30 walk.

Jim: Yeah, you're welcome, Doug. Thanks. Good questions. You know, first on the cadence of SG&A spend. I think it's going to be pretty flat through the course of the year. And obviously, there'll be some variance, but the market development work that we're doing with 3.831, you know, some of which we spent in 2019, we'll continue to do that appropriate education of the disease state area in 2020, but really through a flat, you know, Cadence, as it were. When it comes to the sales force, I think we're still working on the exact sizing. There certainly is overlap between the targets that we are calling on now with our roughly 200 people in the Aristotle field force. You know, I think we're talking in the range of 100 to 200 people, not 400 to 500 people, when you're looking at launching an oral product.

Yeah, you're welcome Doug. Thanks, good questions first on the cadence divest DNA spend I think it's going to be pretty flat through the course of the year and obviously there'll be some variance but.

Market development work that we're doing with three to one you know.

Some some of which we spent in 2019 will continue to do that appropriate education of the disease state area in 2020, but really through a flat.

[music].

Cadence as it were when it comes to the Salesforce I think we're still working on the exact sizing there certainly is overlap between the targets that we that we are.

Calling on now with our roughly 200 people with the Aristada Field Force I.

I think we're talking in the range of 100 to 200 people not.

400, 500 people as Youre looking at launching an oral product. So you know those venn diagrams overlap. So certainly roughly 50 50 terms of the targets with the high value prescribers and certainly institutions that are using Elliott has also use.

Jim: So, you know, those Venn diagrams overlap, you know, certainly roughly 50-50 in terms of the targets with the high-value prescribers and certainly institutions that are using LAIs also use, would use oral agents and would be logical targets for that. But we'll give some more specificity on that as we do more fieldwork and research and come to exact decisions about how large our sales force would be. But hopefully, that gives you some parameters in terms of size. Okay, great. Thanks.

Would use oral agents and be logical targets for that but we'll give some more specificity on that as we do more field work in research.

And come to exact decisions about how large are salesforce would be but hopefully that gives you some parameters in terms of size.

Paul Andrew Matteis: Okay, great. Thank you very much. You're welcome. Our next question is from the line of Paul Matteis with Stiefel. Please proceed with your question. Hey, thanks, guys. This is Nadon for Paul.

Okay, great. Thank you very much.

You're welcome.

Our next question from the line of policies with Stifel. Please proceed with your question.

Hi, Thanks, guys as net on for Paul to two questions. Maybe on obviously that is a business first off.

Nadon: Two questions, maybe on opposite ends of the business. First off, on Aristocratic Gross to Nets, it seems like I've heard you talk in the past about being able to hold kind of steady around the 50% range. Is that a reasonable assumption still, or can we expect it to continue to slide up maybe a percent or two a year? And then, secondly, maybe if you could just, I know it's very early, but provide us with an update on the HDAC platform and where you are with candidates and when you think you might be able to hit humans or how IND-enabling studies are going.

On airside gross to nets. It seems like I've heard you talk in the past about being able to hold.

End of steady around the 50% range is that a reasonable assumptions still or can we expected to continue to slide out may be a percent or two a year and then secondly, maybe if you can just I know, it's very early but provide us with an update on H. DAC platform and where you are with candidates and.

When you when you think you might be able to humans are how R&D, enabling studies are going thanks.

Sure.

Jim: Sure, I'll take the first one and then Rich can answer the one about Rodana and the HDAX. In terms of gross nets with Aristotle, you know, we did see a change this year. I think two things really drove that. There was a consolidation, which I would say is probably a one-time consolidation among the large insurers in the United States, you know, Aetna, CVS, etc. That really drives managed Medicaid business in the various states and so with larger

Ill take the first one and then rich can answer the one about Rodin.

And the HX in terms of gross to nets with ARISTOTLE, we did see a change this year I think two things really drove that there was a consolidation, which I would say is probably a onetime consolidation.

In the of the large insurers in the United States Adnan Cvs.

Et cetera.

That really drives.

Managed Medicaid business in the various states and so with larger buying power.

Jim: The other part is the increasing opportunity we see in the VA, so I think it's hard to predict how those things will change in 21 and beyond. So I would say modeling it at 52% is appropriate for 2020. I wouldn't necessarily tick it up beyond that in future years because that consolidation is more of a one-time thing, and the growth might be related to our growth in the VA, but hopefully, we can offset that with growth in broader parts of the lower growth to net part of the business separate from the VA, if that makes sense.

Yeah that affected our gross so thats a little bit so the other part is the increasing.

Opportunity, we see in the VA, So I think it's hard to predict.

How those things will change in 21 and beyond but I think that so I would say modeling at 52% is is appropriate for 2020, I wouldn't necessarily ticket up beyond that in future years, because that consolidation is more of a onetime thing.

The growth might be related to our growth in the VA, but hopefully we can offset that with growth in broader parts of the.

Of the lower gross to net part of the business separate from the VIP that makes sense.

Richard F. Pops: I'll take the question on the HDACs because I know you guys have a lot of background on where Rodin was in their development. It's really interesting to see when you take it out of the context of the small venture-backed company and put it into our capabilities, which much broader chemistry as well as formulation and biology capabilities. We're running hard now on three parallel tracks. Rodan was focused primarily on the large synaptopathies that we talked about, primarily Alzheimer's disease. We are as well, but we've expanded that now to include accelerating the FTD program, the progranulin program, as well as looking at opportunities in oncology. So we're doing IND-enabling work in that first category, and perhaps in the second category; we hope to nominate a candidate by year end.

I will take I'll take the question on the on the H. tax because I know you guys have a lot of background with that with were wrote down was in their development.

It's really interesting to see when you take it out of the context of the small venture backed companies put it into our capabilities, which from a much broader chemistry as well as formulation in biology capabilities. We're running hard now on three parallel tracks ROADM was focused primarily on the on the large kind of top of DC, we talked about primarily.

All times disease, we are we are as well, but we've expanded that now to include accelerating the FTD program. The program one program as well as looking at opportunities in oncology.

So we're doing in India, enabling work in that first category.

And protect perhaps in the second category, we hope to nominate a candidate by year end.

Richard F. Pops: Great. Very helpful. Thanks, guys. You're welcome.

Great very helpful. Thanks, guys.

Welcome.

Our next question is from the line of a cash to white with Wolfe Research. Please proceed with your question.

Akash Tewari: Our next question is from the line of Akash Tewari with Wolf Research. Please proceed with your question. Hey, hey guys, thanks so much for taking my questions.

Hey, Hey, guys. Thanks, so much for taking my questions. So I wanted to maybe reconcile.

Akash Tewari: So I wanted to maybe reconcile some of the comments you were making on R&D spend with what we kind of had in 2019. And I know that the K isn't out yet. So I'm going to extrapolate a bit. But for 3831, let's just say that for your external R&D, there's 31 million, Bumerity 30 million, 5461, 20 million, 4230, 34, and then the other external R&D programs, about 70 million. If we're going to take down the IL-10 spending, it looks like for 3831 boomerity and 5461, that should at least decrease over time. Is it fair to say that if consensus is kind of modeling, flattish R&D spend over the next few years, you do have some optionality here where it could be a bit lower than what we're kind of modeling at the moment. And then on boomerity expectations, and I guess maybe this is a better question for Baijin. But given the TechFedera IP win, how should we kind of think about how their switch strategy evolves? And I noticed there's not that much bacon for Boomerity Estimates in the 2020 guidance. How should we think about that evolving over time?

Some of the comments you are making on R&D spend with what we kind of had in 2019 and I know that the K isn't out yet so I'm going to extrapolate a bit but for 30 31, let's just say that for your external R&D Theres 31 million.

Meredith 30 million five or six 120 million.

40, 230, 34, and then the other external R&D programs about 70 million.

If we're going to take down the aisle 10 spending it looks like for 30 31, do merdian five or six one that should at least decrease over time is it fair to say that if consensus is kind of modeling flattish R&D spend over the next few years you do have some optionality here, where it could be a bit lower than what where kind of modeling at the most.

And then on.

On to marry expectations and I guess, maybe this is a better question for Biogen.

But given the tech their IP wind, how should we kind of think about how their switch strategy evolves and I noticed there's not that much baked in for Mary estimates I guess in the 2020 guidance how should we think about that evolving over time. Thanks a lot.

Akash Tewari: Thanks a lot.

You're welcome good questions.

Richard F. Pops: You're welcome. Good questions. I think what I would say about the spend shift between 2019 and 2020 in R&D is that, you know, you're right. Certain things, obviously, like 5461 and Vumerity will be coming down. I think the place where we're focused going forward to a large degree is 4230 and the expansion there. It is hard to predict just how fast the patients will accrue and exactly what course in each of the therapies that they'll take, and how long they will stay on therapy. And obviously, if, you know, if it's a study in combination with Pembro, that's quite expensive because right now we're purchasing Pembro on our own, and I think appropriately so as we gather more data there. So the real toggle in 2020 and beyond will be 4230, and that'll depend, again, on the breadth of the program that we have and whether we're spending on it alone or potentially with a

[music].

I think what I would say about the spend shifts between 2019 in 2020 in R&D is that.

You are right certain things, obviously like five or six one Andrew Marty will be coming down I think the place where we're focused going forward to the large degree is 40 230 and the expansion. There. It's just it is hard to predict just how fast the patients will accrue and exactly what course in each of the therapies that they'll take how long will.

They stay on therapy, and obviously, if you know if it's a study in combination with Pembro, that's quite expensive because right now we're purchasing pembro on our own I think appropriately so as we gathered more data there. So the real toggle in 2020 and beyond will be 40, 230, and that'll depend again on the breadth of the program that we have an and whether we're spending.

Got it alone or potentially with the partner I would say importantly to note, though there is an ongoing study or an early an illness study for treasury, one which is that grows that will take it out so that spending for three to one is not going to be decreasing.

Richard F. Pops: I would say, importantly to note, though, there is an ongoing study, an early and illness study for 3831, which as that grows, that'll take, you know, so that spending for 3831 is not going to be decreasing as much as you might think if you just said, well, the NDA is filed, and so, you know, R&D will tail down on 3831. So, you know, we look every year as we make investments in R&D, and we'll continue to drive our focus on profitability but also invest in the pipeline, which can really drive the top line, which is going to get us to where we want to be in the long term.

As much as you might think if you just said while the NDA filed in so R&D will will will tail down on three athree. One so we look every year.

As we make investments in R&D and.

We will continue to drive.

Our focus on profitability, but also investing in the pipeline, which can really drive the topline, which is going to get us to where we want to be in the long term.

Richard F. Pops: And this is Rich on the Numeracy. You anticipated my response because I really do think Biogen are the right ones to ask, but I'll give you my two cents on it, which is that I don't think the IPR victory changed the switch strategy. I think early entry of generics might have, but I think the basic strategy has been to focus on new starts and let the differentiating features of the product reveal themselves over time. So we were pleased with that decision because it just gives a little bit more time for the organized launch and introduction of Numerity as a next-generation product. And I think that with patent life into the 30s, there are a lot of reasons to evolve this market toward Numerity.

And this is rich on the new Mary you anticipate in my response, because I really do you think biogen or the right. Once asked I'll give you my two cents on which is I don't think at the IPO. Our victory change the switch strategy I think I think early entry of generics might have.

But.

I think the basic strategy has been to focus on new starts.

And.

Let the differentiating features of the of the product reveal themselves over time. So we were pleased with that decision because it just gives a little bit more time for the for the organize launch in introduction of the Marriott.

Next generation product and I think that with patent life it into the Thirtys.

There's a lot of reasons to to evolve this market toward toward remarrying.

Marc Harold Goodman: Thank you so much. Thank you. Our next question is from the line of Mark Goodman with SVB Lyrinc. Please proceed with your question.

Thank you so much.

Thank you. Our next question is from the line of Marc Goodman with SVB Leerink. Please proceed with your question.

Good morning couple of questions first of all rich can you give us a flavor and what's going on behind the scenes in the oncology business, excluding 40 230.

Marc Harold Goodman: Morning, a couple questions. First of all, Rich, can you give us a flavor of what's going on behind the scenes in the oncology business, excluding 4230, what you guys are doing, whether it's molecule-specific or just broad changes that are going on behind the scenes? And just to piggyback on the last question, maybe you could just give us a sense of how much...

What do you guys are doing whether its molecule specific or just broad.

Changes that are going on behind the scenes and just to piggyback on the last question. Maybe you could just give us a sense of how much you will be spending on 40 230. This year in the R&D budget I mean, we talking to $100 million, we talking more than that.

Marc Harold Goodman: You'll be spending 4230 this year in the R&D budget. I mean, we're talking $100 million.

Marc Harold Goodman: We're talking more than that. And then, second of all, Vivitrol, can you give us a sense of how much of the business today is alcohol versus opioids? Thanks. More to mark, I'll take the first. I'll take the first, and I'll let Jimineen on the second too.

And then.

Second of all.

Vivitrol can you give us sense of how much of the business today is alcohol versus opioids. Thanks.

More to Mark I'll take the first I'll take the first and I'll let.

Jimmy.

Second too.

There is there's a couple of different areas, we've talked about publicly on the oncology side that we're excited about one.

Richard F. Pops: There are a couple different areas we've talked about publicly on the oncology side that we're excited about. One is embodied in the IL-2 program, which is this idea of engineered cytokines. And the ability that we have to engineer... Proteins as well as antibody constructs in oncology exploiting known features of cytokines is, hopefully, that will continue to bear fruit for us, with the caveat that Umer raised on aisle two, on aisle ten, but we have some other things cooking in the labs as well. The other one is HDACs in oncology. Particularly the most immediate adjacency, what we're doing with the co-rest complex targeted HDACs is for neuronal-specific brain penetrant HDACs in things like neuroblastoma, medulloblastoma, glioblastoma. So those programs are active right now and we'll see where they go, but the pharmacology of HDACs as oncolytic agents is established. And then we have some other small molecule stuff going on in the labs that we haven't disclosed, but hopefully, we'll get to the point where it's worth talking about in the future.

Is embodied in the in the two program, which is this idea of engineered cytokine and our way we the ability that we have to engineer.

Proteins as well as is antibody constructs in oncology.

Sporting known features of.

Cytokine says is hopefully that will continue to bear fruit for us.

With that with the caveat that number raise on.

Ill to 10.

But we have some other things cooking in the labs as well the other one is is HX and oncology.

Particularly the most immediate Jason C.

What we're doing the co rest complex targeted h. tax is for neuronal specific being brain penetrant h. decks in things like neuroblastoma Megill Blastoma glioblastoma. So those those programs are active right now and we'll see.

Where they go but that pharmacology, obviously for four as HDT accident Oncolytic agents is established and then with some we have some other small molecule stuff going on as we haven't disclosed, but hopefully we'll get to the point, we're it's worth talking about.

In the future.

Jim: And then I think for R&D spend on 4230 in 2020, we're anticipating an increase as compared to where we were in 2019. I think overall about 20% of the total R&D budget would be focused on external expenses related to 4230. And then, in addition to that, we obviously have an internal team of people working on the program as well.

I think for R&D spend for 40, 230, and Twentytwenty, we're anticipating an increase as compared to where we were in 2019 I think overall about 20% of the total R&D budget would be focused on external expenses related to 40 239. In addition to that we have obviously an internal team.

With people working on the program as well so that'll give you a sense as to how much was spending in the.

Richard F. Pops: So that'll give you a sense as to how much we spend in a year. And then, Mark, in terms of the alcohol-opiate split, it's a good question. And, you know, as you know, the only way we can really get a look at that is through the prescriptions that come through our hub. That's about 30% of our business. And if you look at that, the actual percentage of alcohol is moving up a little bit. And we predict now that it's about 60-40, with opiate alcohol being around 40%. Again, that's in the business through the hub. So it's a little hard to extrapolate on the whole business, but that's the sense that we have, and that's why we're focused on trying to drive additional growth in alcohol in 2020.

And then mark in terms of the alcohol opiates split it's a good question and and as you know the the only way we can really get a look at that is through the prescriptions that come through our hub, that's about 30% of our business and if you looked at that the actual percentage of alcohol is moving up a little bit and we predict now that it's about 60 40.

Opiate alcohol being around 40% again thats in the business through the hub so its little hard to extrapolate on the whole business, but thats. The since that we have and that's why we're focused on trying to drive additional growth and alcohol in 2020.

Thanks.

Emil Devon: The next question is from the line of Emil Devon with Mizzouho. Please proceed with your question. Great, thanks for taking my question. So one on 3831, just as we're sort of getting closer to potential approval here, can you share any updated thoughts around the interactions you have with payers? I think there are a lot of questions there in terms of the steps patients might have to go through in terms of getting on therapy. And I guess, specifically, the questions around whether there will be a need for patients to take a generic version of Zyprexa before they'd be able to take 3831. So, any updated thoughts you can share would be helpful. And then the other one is just on Aristotle.

Welcome.

I would ask questions from the line of a meal Devons with Mizuho. Please proceed with your question.

Great. Thanks for taking my question. So one on 30 831.

Just as we're sort of getting closer to potential approval here can you share any updated thoughts around generations have a payers that a lot of questions. There in terms of.

Steps patients may actually go through in terms of getting on therapy.

I guess, specifically the questions around will there be a need for patients to take a generic version as a Brexit.

Where they'd be able to take 30 31, so any updated thoughts you can share would be helpful and another one just on air started just curious initiate has been on the market for little while now just maybe just some updated thoughts in terms of the impact that add on patients starting.

Richard F. Pops: Just curious, an issue that's been on the market for a little while now. Maybe just some updated thoughts in terms of the impact that it has had on patients starting, and has it had the impact that you expected when you launched that version. Thanks.

Been had the impact expected when you when you launch that version thanks.

Richard F. Pops: Morning, Bob, I'll take those. The first round of interactions with payers in 2019 was more general about how would you position and treat a new branded on call it anti psychotic agent. And, and so Actually, it's surprisingly not a lot of questions. We know exactly what will happen because we've been in this market with Aristotle for so long, which is that patients don't get access to branded medicines until they fail on generic medications, often more than once. The specific answer about a step through on olanzapine, I don't think we'll have a definitive answer on that until we're able to present the clinical data and the label from our as we complete the interactions with FDA. We expect that there's a strong medical rationale not to force patients to gain weight or have metabolic perturbances as they cycle through olanzapine.

One of them all I'll take those.

The first round of interactions with payers in 2019 was more general about how would you position how would you treat and new branded oncology.

Psychotic agent.

And.

And so.

Actually it's surprisingly non there aren't a lot of questions. We know exactly what will happen in the because we've been in this market with aerostar.

Patients don't get access to branded metal until they fail on generic medications often more than once.

The specific answer about a step through on Atlanta, I don't think we'll have a definitive answer on that until we're able to present, the clinical data and the label.

From from our actually as we complete the interactions with FDA, we expect that.

There is a strong medical rational not to have fourth patients to gain weight or have metabolic for turbines is as the as the cycle through lands that means but being the way. The world is in schizophrenia I would imagine the end of the day, we will have a range of different access restrictions by various plans ranging from very open acts.

Richard F. Pops: But being the way the world is in schizophrenia, I would imagine at the end of the day, we'll have a range of different access restrictions by various plans, ranging from very open access to very restrictive access. But we'll, like we did with Aristota, sequentially seek to knock those down over time. But we know going in, and anybody launching into the schizophrenia market should know that you're going to be stepped through generic medications before patients get access to branded medications. And the countervailing force, of course, is that just almost everybody cycles through multiple generic medications, and there's a tremendous amount of unmet need out there. In our case, we really feel like the principal unmet need is efficacy, and that's what we're bringing.

Yes, two very restrictive access, but will like we did with ARISTOTLE will sequentially seek to knock those down overtime, but we know going in and anybody launching in this into the schizophrenia for any market should know that youre going to be you're going to be stepped through generic medications before patients get access to branded medications and the counter.

Selling force of course is that just almost everybody does that cycled through multiple generic medications and there's a tremendous amount of unmet need out there in our case, we really felt that the principal unmet need is efficacy.

And that's what that's where we're bringing.

Jim: Yeah, great. Hi, it's Jim.

Yes, great.

Jim: In terms of initio and its impact on launch, I would say that, you know, initio is very much related to our two-month dosage form. That's the focus that we are educating the market on, and I think that we're getting a nice response from the market. And the two-month is growing very nicely. It's now over 30% of our total scripts, and that's directly related to initio. So that's a major differentiation between the other LAIs, as you know, to be able to come in and start in a matter of days and, you know, leave your place of therapy with two months of medication on board with Aristata is a very, very important opportunity for patients and physicians. So I'd say initio tied to two months, that growth is really going quite nicely, and we expect that to continue to grow.

Oh, Hi, it's Jim in terms of the.

Initio and its impact on launch I would say initiate a very much related to our two month dosage form thats. The focus that we are.

Educating the market around and I think that we're having a nice response from the market.

And the two month is growing very nicely, it's now over 30% of our total scripts and thats directly related to initio. So that's a major differentiation between the other Elie eyes as you know to be able to come in and start.

In a matter of days and leave Sarit leave you are places therapy with two months of.

Medication onboard with ARISTOTLE is a very very important opportunity for patients and physicians. So I'd say initio tied to two month that growth is really going quite nicely and we expect that to continue to grow.

Richard F. Pops: In fact, I'll put a finer point on that even for Yvonne Moulton, that the marketing message for Aristata, as it's evolved from its original approval through the approval of the multiple elements of the product family in 2020, it's very much focused on what Jim just said, initio plus two months. It's a really differentiated offering in the marketplace. It's six injections, six interventions across the year. You can provide therapeutic concentrations of a very well-tolerated, highly efficacious medicine. That regimen was supported by a large phase three study called Alpine, which we unblinded in the middle of last year. All roads are pointing toward right now the clarity of the message around initio and two months.

In fact, I'll put a finer point of that even before you have almost to the marketing message for aerostar as it's evolved from its original approval through the approval of the multiple elements of the product family in 2020, it's very much focused on what Jim just set initio plus two month, it's a really differentiated offering in the marketplace at six injections.

Six interventions across the year.

And you can provide therapeutic concentrations of a very well tolerated highly efficacious medicine and natural gas regimen was supported by a large phase three study called Alpine, which we which we unblinded in the middle of last year. So all roads reporting pointing toward right now the clarity of message around initio into month.

Okay. Thanks.

Richard F. Pops: Okay, thanks. Thank you.

Thank you. The next question is from the line of Terence Flynn with Goldman Sachs. Please proceed with your questions.

Terrence Flynn: The next question is from the line of Terrence Flynn with Goldman Sachs. Pleased to see you with your question. Hi, this is Holly Barrow on behalf of Terrence. Thanks so much for taking the question. One on 4230, what would you like to see from the ongoing combination trial to advance the drug forward and continue to invest resources there? Thanks so much.

Hi, This is high barrier on for Karen. Thanks, So much for taking my question one on June 30.

From the ongoing combination trial to advance the drive forward and.

Continue to invest resources there. Thanks, so much.

Richard F. Pops: I think you could probably answer that question yourself. What we want to see is the efficacy of this medication. We've already demonstrated its biological activity and tolerability profile of it, and now we're investigating its efficacy as an oncology agent in a number of different settings, both as monotherapy and then in combination with, at the moment, an IO agent like Pembrolizumab, both in settings where PEMBRO is approved and in settings where PEMBRO by itself has not been approved. So what we're hoping is that 4230 can unlock additional biological potential of the PD-1s and also open up new areas of cancer treatment that are currently unavailable to patients if they're looking for treatment with PD-1s. Then, beyond that, we think that 4230 can be an effective combination agent with a number of other non-IO agents as well across a number of different treatment settings and lines of therapy. So we have a lot to learn about 4230, and what's so encouraging to us is that the basic hurdles that we set for ourselves in advance to get over, to convince ourselves that we have an active agent here, we are sequentially crossing each of those hurdles successfully. So I think our optimism is growing.

I think you could probably answer that question yourself I think we.

We want to see is is.

The efficacy of this medication, we already have demonstrated the backlog biological activity and Tolerability profile of it now we're investigating its efficacy is as an oncology in a number of different settings, both as monotherapy and then in combination with at the moment I O agent like client Pembrolizumab.

Both in settings, where pembro was approved and in settings, where pembro by itself has not been approved. So we're hoping is at 40 230 can unlock additional biologic potential of the PD ones and also open up new areas of cancer treatment that are currently unavailable to patients if they're looking for.

For treatment with PD ones, then beyond that we think that that 40 230 can be an effective combination agent with a number of other non io agents as well across a number of different treatment settings and lines of therapy. So we have we have a lot to learn about 42 journey, so encouraging to us is that.

The basic the hurdles that we set for ourselves in advance to get over to convince ourselves that we have an active agent here, we are sequentially crossing each of those hurdles successfully so.

I think our optimism is growing.

Sandra Coombs: We have time for one more question, please, Rob. Hi. Yes, the question will be coming from the line of Danielle Brill with Piper Jaffray. Hi guys. Good morning. Thanks for the question. Just a quick follow-up on the HDoC platform. Curious how you're thinking specifically about the FTD opportunity, considering gene therapy approaches targeting progranulin are already entering the clinic. I may have missed this, but how soon do you think you could get your progranulin program into the clinic? Thanks.

We have time for one more question please Rob I.

You asked a question will be coming from the line of Daniel belt with Piper Jaffray.

Hi, guys. Good morning. Thanks for the question just a quick follow up on the stock platform curious, how you're thinking specifically about the FTD opportunity considering gene therapy approaches targeting programming line are already entering the clinic and I may have missed this but how do you think you could get.

Granular program into the clinic. Thanks.

Danielle Brill: Good morning, Danielle. Good questions, because the FTD program is one that I'm not ready to say that we've got a horse in this race yet. I know that we have a really strong hypothesis and the chemistry is promising. But I think our scientists would make the argument that it's not clear that the gene therapy approach would be necessarily superior to a small molecule, a well-tolerated oral small molecule, given the regional distribution in the brain of where you might want progranulin expression. So if we can, if we have highly penetrant drugs that are both driving progranulin, as well as increasing synaptogenesis, that could be very interesting, but I think there's still plenty of risk here, so I'm not ready to be ready to say that we were better or worse than anybody else.

Yes, good morning, Daniela good good questions because the FTD program is one that I'm not ready to say that we've got to a horse in this ratio I noted we have a really strong hypothesis and the chemistry is promising and I could I think our scientists would make the argument it's not clear that gene therapy approach.

Would be necessarily superior to a small molecule well tolerated oral small molecule given the the regional distribution in the brain, where you might want programming Lynn expression. So if we can if we have highly penetrant drugs that are up both driving program anyone as well as.

Increasing snap to Genesis that could be very interesting, but I think there's still plenty of risk here, so I'm not ready to be ready to say that we were better worse anybody else.

Understood. Thank you.

Richard F. Pops: Thank you. Thank you.

You're welcome.

Thank you we've reached the end of the time allotted for today's question and answer session. I will now turn the call over to Sandy homes for closing remarks.

Sandra Coombs: We've reached the end of the time allotted for today's question and answer session. I will now turn the call over to Sandy Coombs for closing remarks. Great. Thank you everyone for joining us on the call today. If you have any follow-up questions, please feel free to reach out to us at the company. This concludes today's conference. You may now disconnect your lines at this time. Thank you for your participation.

Great. Thank you everyone for joining us on the call today. If you have any follow up questions. Please feel free to reach assets at the company.

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