Q4 2023 Neurocrine Biosciences Inc Earnings Call

February 7, 2024

Operator: Good day, and welcome to Neurocrine Biosciences year end and 4th Quarter results call. At this time all participants are in a listen only mode. Later, you will have the opportunity to ask questions during the question and answer session. You may registered to ask a question at any time by pressing star one on your telephone keypad. You may remove yourself by pressing star two. Please note today's call will be recorded and I'll be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

At this time all participants are in a listen only mode.

Later, you will have the opportunity to ask questions. During the question and answer session me.

Any registered to ask a question at any time by pressing star one on your telephone keypad.

You may remove yourself by pressing star two.

Please note today's call will be recorded and I'll be standing by if you should need any assistance.

It is now my pleasure to turn the conference over to Todd touched luck Vice President of Investor Relations. Please go ahead.

Todd Tushla: Thank you and good one day morning to everyone. Welcome to Neurocrine Biosciences 4th quarter and full year 2023 earnings call. Joining us today are Kevin Gorman, Chief Executive Officer, Matt Abernethy, Chief Financial Officer, Eiry Roberts, Chief Medical Officer, Eric Benevich, Chief Commercial Officer, and Kyle Gano, Chief Business Development and Strategy Officer. During the call we will be making forward looking statements. These statements are subject to certain risks and uncertainties and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. Today's prepared remarks will be a bit longer in duration versus prior earnings calls, as we do have a lot of ground to cover. I can assure you that we will do our best to address all of your questions when we get into Q&A. So now, I'll turn the call over to Kevin.

Joining us today are Kevin Gorman, Chief Executive Officer, Matt Abernethy, Chief Financial Officer, IV Roberts, Chief Medical Officer, Eric benefits, Chief Commercial Officer, and Kyle Gano, Chief business development and strategy Officer.

During the call we will be making forward looking statements. These statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to review the risk factors discussed in our latest SEC filings.

Today's prepared remarks will be a bit longer in duration versus prior earnings calls as we do have a lot of ground to cover I can assure you that we will do our best to address all of your questions. When we get into Q&A. So now I'll turn the call over to Kevin.

Kevin C. Gorman: Thank you, Todd and good morning, everyone. So, we had a great 2023, I said the same thing about 2022 and it was great. I said there are very few years you'd get like 2022 and we then had one of those years in 2023. Most of those years were not without their ups and downs, but on the whole, the business performed exceptionally well. I mean, looking at 2023 - again, incredible continued growth for INGREZZA in its sixth year on the market. Expansion for INGREZZA intellectual property out to 2038. Approval of INGREZZA and another indication in Huntington's disease. We also had CRINECERFONT Phase III data that beat even our highest expectations for that. And a clinical pipeline that grew more in that one year than we've ever experienced at Neurocrine in the past. And then, a preclinical pipeline that is growing quite a bit. Now, we expect an equally successful 2024. And I'm not going to go into the details of that because my colleagues in the room are going to talk about that. But right now, let's take a snapshot of 2023 from a financial perspective, from Matt and he will also give you how we're viewing 2024. Matt?

So.

We had a great 2023, I said the same thing about 2022 and it was great. I said there are very few years you'd get like 2022, and we then had one of those years in 2023.

Most of those years, we're not without their ups and downs, but on the whole the.

Business performed exceptionally well.

I mean looking at 2020 three.

Again incredible continued growth for <unk> grants in its sixth year on the market expansion.

[laughter] grandson.

Intellectual property out to 2038 approval of an grandson and another indication in Huntington's disease.

We also had <unk> phase III data does that and beat even our high expectations for that and a clinical pipeline that grew more in that one year than we've ever experienced at neurocrine in the past.

And then a preclinical pipeline that is growing quite a bit.

Now we expect.

Equally successful 'twenty 'twenty, four and I'm not going to go into the details of that because my colleagues in the room are going to talk about that but right now, let's take a snapshot of <unk> of 2023 from a financial perspective.

From that and he will also give you how we're viewing 2020 for Matt.

Matthew Abernethy: Thanks, Kevin. Good morning. 2023 was an incredible year, record in graduate sales growth, positive CRINECERFONT results and in advancing our R&D pipeline. All positioning us for continued progress for years to come. Further jumping into our 2024 financial guidance, I wanted to provide a few comments associated with our 2023 financial performance. First, INGREZZA sales performance; during the fourth quarter, INGREZZA sales were $500 million, reflecting continued sequential growth, driven by new patients slightly offset by gross to net dynamics. 2023 INGREZZA sales finished near $1.84 billion, reflecting over $400 million in year-over-year growth. Next, one of our goals for 2023 was to demonstrate SG&A financial leverage. As you can see, we delivered approximately 400 basis points and 300 basis points of SG&A leverage on a GAAP and non-GAAP basis, respectively. We expect continued progress in 2024, which I'll discuss shortly. Finally, we generated over $600 million of cash flow in 2023, reflecting strong, non-GAAP net income, partially offset by $175 million in business development investment. Turning to 2024, this will be another pivotal year for Neurocrine with growing and growth of sales, preparing for the commercial launch of CRINECERFONT and the many activities associated with advancing our R&D portfolio, which were highlighted at the recent analyst day. We believe investing in these areas will continue to drive long term shareholder returns.

Positioning us for continued progress for years to come.

Her did jumping into our 'twenty 'twenty four financial guidance I wanted to provide a few comments associated with their 2023 financial performance.

<unk> sales performance during the fourth quarter and gross sales were $500 million, reflecting continued sequential growth driven by new patients slightly offset by gross to net dynamics 2023 and Brexit sales finished near $1.84 billion, reflecting over 400 million.

Dollars in year over year growth.

Next one of our goals for 2023 was to demonstrate SG&A financial leverage as you can see we delivered approximately 400 basis points and 300 basis points of SG&A leverage on a GAAP and non-GAAP basis, respectively.

We expect continued progress in 2024, which I'll discuss shortly.

Finally, we generated over $600 million of cash flow in 2023, reflecting strong non-GAAP net income, partially offset by $175 million in business development investment.

Turning to 2024 this will be another pivotal year for neurocrine with growing and growth of sales preparing for the commercial launch of pronounced are fine and the many activities associated with advancing our R&D portfolio, which were highlighted at the recent analyst day.

We believe investing in these areas will continue to drive long term shareholder returns.

Matthew Abernethy: Now onto our 2024 financial guidance. 2024 and gross and net sales guidance is $2.1 to $2.2 billion, reflecting strong underlying demand and an improving gross to net resulting in over $300 million of sales growth or 17% at the midpoint. As always, we expect seasonal dynamics to play out similar to what we've seen in previous years. 2024 SG&A GAAP operating expense guidance is $930 million to $950 million or 43% of total revenues at the midpoint. And $830 to $850 million, or 39% of total revenue at the midpoint, on a non-GAAP basis. These costs reflect continued investment in INGREZZA and also an incremental $50 million to prepare for the potential CRINECERFONT launch, as Eric will discuss shortly. Even with the investment in CRINECERFONT, we expect to demonstrate 400 basis points and 150 basis points in an SG&A GAAP and non-GAAP leverage, at the midpoint of the range. As you develop your models, we do have a seasonal nature tourist's spending, specifically a step up in Q1. 2024 R&D GAAP operating expense guidance is $645 to $675 million, or 30% of total revenue at the midpoint. And $570 million to $600 million, or 27% of total revenue at the midpoint on a non-GAAP basis. These costs reflect investment in our ongoing 17 clinical programs, including our CRINECERFONT studies, muscarinic programs and early stage pipeline highlighted at analyst day.

2024, and gross and net sales guidance is 2.1 to $2 $2 billion, reflecting strong underlying demand and an improving gross to net resulting in over $300 million of sales growth or 17% at the midpoint.

As always we expect seasonal dynamics to play out similar to what we've seen in previous years.

'twenty 'twenty four SG&A GAAP operating expense guidance is $930 million to $950 million or 43% of total revenues at the midpoint and.

These costs reflect continued investment in browser and also an incremental $50 million to prepare for the potential kronos or pontoon launch as Eric will discuss shortly.

Even with the investment in Kronos or plant, we expect to demonstrate 400 basis points, and 150 basis points and SG&A GAAP and non-GAAP leverage at the midpoint of the range.

As you develop your models, we do have a seasonal nature tourist's spending specifically a step up in Q1.

2024, R&D GAAP operating expense guidance is $645 $675 million or 30% of total revenue at the midpoint.

And $570 million to $600 million or 27% of total revenue at the midpoint on a non-GAAP basis.

These costs reflect investment and our ongoing 17 clinical programs, including our <unk> studies muscarinic programs.

The early stage pipeline highlighted at analyst day.

Matthew Abernethy: Note this guidance range does not include any partnership milestone payments until they are deemed probable. A few other financial metrics to note: We expect cost of revenue to be 2% of sales. Stock based compensation is expected to be $175 million with the $100 million in SG&A and $75 million in R&D. We expect our non-GAAP effective tax rate to be around 23%. As I reflect about the journey we've been on over the past five years. It is quite remarkable. With INGREZZA now trending above $2 billion in sales, the next leg of growth [inaudible] with CRINECERFONT. And advancing pipeline into strong financial profile, we are well positioned for the future and feel quite fortunate. With that, I now hand the call over to Eric Benevich, our Chief Commercial Officer. Eric.

A few other financial metrics to note.

We expect cost of revenue to be 2% of sales stock.

Stock based compensation is expected to be $175 million with the $100 million in SG&A and $75 million in R&D.

We expect our non-GAAP effective tax rate to be around 23%.

As I reflect about the journey, we've been on over the past five years. It is quite remarkable with <unk> now trending above 2 billion in sales. The next leg of growth to our story with Chronister bond and advancing pipeline into strong financial profile, we are well positioned for the future and feel quite fortunate.

With that I now hand, the call over to Eric benefits, our Chief commercial Officer Eric.

Eric Benevich: Thanks, Matt. 2023 marked another stellar year for INGREZZA and included several important milestones for the franchise. This includes the continued increase in diagnosis and treatment rates for patients with tardive dyskinesia. The addition of a new indication for chorea, associated with Huntington's disease. And the end of litigation settlement that provides exclusivity for 14 more years out to 2038. 2023 was our sixth year in the market since launch. While full year sales growth of nearly 30% is impressive, that growth speaks volumes about the continued unmet need in both PD and HD Chorea. Looking ahead, we still have a tremendous opportunity to help many more patients. While we continue to make steady progress, two thirds of the approximately 600.000 TD patients in the U.S. remain as yet undiagnosed. And for the approximately 20.000 HD patients with moderate to severe chorea, 80% are still not being treated with a VMAT2 inhibitor. The only FDA approved class of medicines for this indication.

This includes the continued increase in diagnosis and treatment rates for patients with tardive Dyskinesia. The addition of a new indication for chorea associated with Huntington's disease.

And the and a litigation settlement that provides exclusivity for 14 more years out to 2038.

2023 was our sixth year in the market since launch while full year sales growth of nearly 30% is impressive that growth speaks volumes about the continued unmet need in both PD and HD Korea.

Looking ahead, we still have a tremendous opportunity to help many more patients. While we continued to make steady progress two thirds of the approximately 600000 TD patients in the U S remain as yet undiagnosed and.

And for the approximately 20000 HD patients with moderate to severe Korea, 80% are still not being treated with a <unk> two inhibitor.

The only FDA approved class of medicines for this indication.

Eric Benevich: This year, our commercial and medical teams will continue to educate and motivate health care providers to screen, diagnose and treat TD and HD chorea patients. In addition, we will continue our efforts to reach patients and caregivers to help them recognize their involuntary movements as possibly TD or HD chorea. And encourage them to talk with their health care provider about diagnosis, and if appropriate, treatment with INGREZZA. Although we have made great progress these past six years, the majority of the opportunity remains ahead of us. The 2024 INGREZZA sales guidance range of $2.1 to $2.2 billion is driven primarily by the pace of new patient starts and TD, and to a smaller degree, in HD where INGREZZA is still in its early launch phase after the approval and launch towards the end of last year. Specific to TD, we anticipate robust growth across all three business segments of psychiatry, neurology and long term care. Access to INGREZZA remains strong, as exemplified by the fact that regardless of formulary status, greater than 80% of written scripts for INGREZZA gets filled and the average out of pocket cost is less than $10. Overall, I'm looking forward to another solid year of growth for the franchise as we continue to build these markets. At this time, we're going to mix things up a little bit versus our normal cadence for prepared remarks. My colleague Dr. Eiry Roberts, our Chief Medical Officer and I are going to provide a CRINECERFONT update. We thought it important to highlight the integrated efforts between our respective organizations to prepare for an anticipated 2025 launch. Eiry, why don't you start?

To talk with their health care provider about diagnosis, and if appropriate treatment with <unk>.

Although we have made great progress. These past six years the majority of the opportunity remains ahead of us the.

The 2024 and aggressive sales guidance range of $2. One to $2 2 billion is driven primarily by the pace of new patient starts and PD and to a smaller degree and HD wherein grants is still in its early launch phase.

After the approval and launch towards the end of last year.

Specific to TD, we anticipate robust growth across all three business segments of psychiatry and neurology.

And long term care.

Access to and graduate remains strong as exemplified by the fact that regardless of formulary status greater than 80% of written scripts for congrats it gets filled and the average out of pocket cost is less than $10. Overall I'm looking forward to another solid year of growth for the franchise as we continue to build these markets.

Eric Benevich: At this time, we're going to mix things up a little bit versus our normal cadence for prepared remarks. My colleague Dr. Eiry Roberts, our Chief Medical Officer and I are going to provide a CRINECERFONT update. We thought it important to highlight the integrated efforts between our respective organizations to prepare for an anticipated 2025 launch. Eiry, why don't you start?

We thought it important to highlight the integrated efforts between our respective organizations to prepare for an anticipated 2025 launch.

Why don't you start.

Eiry W. Roberts: Thanks, Eric, and good morning, everyone. Let me start by reminding everyone of the incredible challenge congenital adrenal hyperplasia patients face today. So, these patients, their only real option lifelong treatment with high dose glucocorticoids is both entrenched and flawed. In this paradigm, GCs are tasked with both replacing the missing cortisol and supressing the excess androgens. Patients therefore face the difficult choice of either taking long term, high dose GC to reduce excess androgens and thus face a long term complications of GC exposure, such as hypoglycemia, dyslipidemia, cardiovascular disease, osteoporosis, psychiatric disturbances or immunosuppression. Or they can try to minimize their GC exposure and live with the consequences of excess androgen production, such as advanced bone age, precautious puberty, short adult stture, irregular menstruation or infertility. These are the difficult tradeoffs patients living with CAH must make every day. With the impressive efficacy and tolerability data from the adult and pediatric registrational studies for CRINECERFONT, we hope to provide a potentially new paradigm for these patients. So, they've been combined efforts between Neurocrine medical and commercial organizations are well underway, as we prepare to bring CRINECERFONT to CAH patients in the U.S. and in key European markets.

So these patients the only real option lifelong treatment with high dose glucocorticoids is both entrenched.

Lord.

In this paradigm gcs are tasked with both replacing the missing cortisol.

Pressing me excess androgens.

Patients therefore faced the difficult choice of either taking long term.

High dose GC to reduce excess androgens and thus faced a long term complications of GC exposure, such as hypoglycemia, dyslipidemia cardiovascular disease, osteoporosis psychiatric disturbances or in munis suppression.

They can try to minimize that GC exposure and live with the consequences of excess androgen production such as advanced bone age Precautious puberty show us adult start yet.

Irregular menstruation oriented Timothy.

These are the difficult tradeoffs patients with living with CAH must make every day.

With the impressive efficacy and Tolerability data from the adult and pediatric Registrational studies for connect the ponds we.

Hope to provide a potentially new paradigm for these patients.

So they've been combined efforts between Neurocrine medical and commercial organizations are well underway as we prepare to bring connect to CAH patients in the U S and in key European markets.

Eiry W. Roberts: Later this year, we look forward to sharing additional safety and efficacy data from the registrational studies in peer reviewed journals and scientific conferences. In addition, our medical affairs to field teams are highly engaged with thought leaders in the field to develop the extensive educational programs necessary to support launch, while our health outcomes team works to generate and publish critical data necessary to characterize the burden of disease in CAH and support the value proposition of CRINECERFONT as an effective treatment for patients living with congenital adrenal hyperplasia. Our key focus now within clinical development and regulatory is on the completion of the new drug application for CRINECERFONT in adults and pediatrics with the FDA. I'm pleased to report that the NDA submission will occur in the second quarter of this year. Recall the agency granted breakthrough therapy designation for CRINECERFONT at the end of last year. This designation serves as an acknowledgment of the serious and life threatening nature of CAH, highlights the significant unmet need that exists in the treatment of the disease with no approved treatment for the past 60 plus years. And identifies CRINECERFONT as a potentially valuable treatment for patients with CAH. While we are hopeful that the granting of breakthrough designation for CRINECERFONT will lead to priority review, that decision ultimately rests with the FDA. So, we are moving forward in a way that proactively prepares us for all eventualities, including the possibility of an advisory Committee. Eric will now cover the preapproval activities within the commercial organization.

In addition, our medical affairs to field teams are highly engaged with thought leaders in the field to develop at the extensive educational programs necessary to support launch while our health outcomes team works to generate and publish critical data necessary to characterize the burden of disease in CAH.

And support the value proposition of connect that bonds as an effective treatment for patients living with congenital adrenal hyperplasia.

Our key focus now within clinical development and regulatory is on the completion of the new drug application for <unk> in adults and pediatrics with the FDA.

I'm pleased to report that the NDA submission will occur in the second quarter of this year.

Recall the agency granted breakthrough therapy designation for connect to fund at the end of last year.

This designation as an acknowledgment of the serious and life threatening nature of CAH highlights the significant unmet need that exists in the treatment of the disease with no approved treatment for the past 60 plus years.

And identifies connect that bond as a potentially valuable treatment for patients with CAH.

While we are hopeful that the granting of breakthrough designation for connect to fund will lead to priority review that decision ultimately rests with the FDA. So we are moving forward in a way that proactively prepares us for all eventualities, including the possibility of an advisory Committee.

Eiry W. Roberts: Eric will now cover the preapproval activities within the commercial organization. Thanks, Larry This is an exciting time for our commercial team as we prepare for the launch of <unk>. If approved <unk> would be not just the first ever CRF antagonist, but also be the first medication specifically approved for the treatment of CAH with <unk>. Presented with the opportunity to build a new market just like the opportunity we had seven years ago, when we set out to launching <unk> as the first medication approved for TD. Building a market for <unk> is a privilege. However, much work remains ahead of US one of our primary areas of focus in 2024 will be education of all stakeholders in the CAH community. This educational effort will focus on disease state awareness challenges with currently available treatment strategies and the recognition of the need for better treatment options. Given the challenges of managing CAH that IV highlighted and the extremely impressive efficacy and tolerability data generated from our phase III studies, we're excited by the potential of <unk> to dramatically change the status quo, we bring forward the possibility of bringing androgens under control while simultaneously reducing. <unk> GC dose to more replacement levels. And the commercial organization, we're ramping up educational efforts directed towards patients parents family members and endocrinologists to help the CAH community better understand the nature of the disease to more fully understand the current unsatisfactory treatment tradeoffs. Between suffering from excess androgen production or the complications of chronic treatment with high dose glucocorticoids. In a compliant way we plan to set the table for a new and simpler approach to treating CAH. It doesn't require the current challenging tradeoffs.

Eiry W. Roberts: Eric will now cover the preapproval activities within the commercial organization.

Eiry W. Roberts: Thanks, Eiry. This is an exciting time for our commercial team as we prepare for the launch of CRINECERFONT. If approved, CRINECERFONT would be not just the first ever CRF antagonist, but also be the first medication specifically approved for the treatment of CAH. With CRINECERFONT, we're presented with the opportunity to build a new market, just like the opportunity we had seven years ago, when we set out to launch INGREZZA as the first medication approved for TD. Building a market for CRINECERFONT is a privilege. However, much work remains ahead of us. One of our primary areas of focus in 2024 will be education of all stakeholders in the CAH community. This educational effort will focus on disease state awareness, challenges with currently available treatment strategies and the recognition of the need for better treatment options. Given the challenges of managing CAH that Eiry highlighted, and the extremely impressive efficacy and tolerability data generated from our Phase III studies, we're excited by the potential of CRINECERFONT to dramatically change the status quo. We bring forward the possibility of bringing androgens under control while simultaneously reducing GC dose to more replacement levels. In the commercial organization, we're ramping up educational efforts directed towards patients, parents, family members and endocrinologists, to help the CAH community better understand the nature of the disease to more fully understand the current unsatisfactory treatment tradeoffs between suffering from excess androgen production or the complications of chronic treatment with high dose glucocorticoids. In a compliant way, we plan to set the table for a new and simpler approach to treating CAH that doesn't require the current challenging tradeoffs.

Thanks, Larry This is an exciting time for our commercial team as we prepare for the launch of <unk>. If approved <unk> would be not just the first ever CRF antagonist, but also be the first medication specifically approved for the treatment of CAH with <unk>.

Speaker Change: Presented with the opportunity to build a new market just like the opportunity we had seven years ago, when we set out to launching <unk> as the first medication approved for TD.

Building a market for <unk> is a privilege. However, much work remains ahead of US one of our primary areas of focus in 2024 will be education of all stakeholders in the CAH community.

This educational effort will focus on disease state awareness challenges with currently available treatment strategies and the recognition of the need for better treatment options.

Given the challenges of managing CAH that IV highlighted and the extremely impressive efficacy and tolerability data generated from our phase III studies, we're excited by the potential of <unk> to dramatically change the status quo, we bring forward the possibility of bringing androgens under control while simultaneously reducing.

<unk> GC dose to more replacement levels.

And the commercial organization, we're ramping up educational efforts directed towards patients parents family members and endocrinologists to help the CAH community better understand the nature of the disease to more fully understand the current unsatisfactory treatment tradeoffs.

Between suffering from excess androgen production or the complications of chronic treatment with high dose glucocorticoids.

In a compliant way we plan to set the table for a new and simpler approach to treating CAH. It doesn't require the current challenging tradeoffs.

Eric Benevich: It will take some time to probably reach and educate educate the CAH patient community, but the good news is that we have already started that process as we prepare for an expected launch in the U S. In 2025, our teams are excited to build another market and bringing a potential new medicine to CAH patients, who sorely need a better option to manage their disease. Yes. Now I'll hand, it back to Irene. Thank you Eric.

Eric Benevich: It will take some time to propperly reach and educate the CAH patient community, but the good news is that we have already started that process, as we prepare for an expected launch in the U.S. in 2025, our teams are excited to build another market and bringing a potential new medicine to CAH patients who sorely need a better option to manage their disease. Now I'll hand it back to Eiry.

Yes.

Now I'll hand, it back to Irene.

Thank you Eric.

Eiry W. Roberts: Thank you, Eric. As we begin the year, Neurocrine pipeline is as broad and diversified as it has ever been and our 32 year history. Importantly, 2024 marks a catalyst rich year. Our Phase II pipeline features several data readouts this year, all of which remain on track for delivery. This includes NBI-845, the AMPA potentiator for major depressive disorder with data in the first half. LUVADAXISTAT, the DAAO inhibitor for cognitive impairment associated with schizophrenia in the second half. And NBI-568 an also [inaudible] M4 agonist for treatment of psychosis and schizophrenia also reading out in the second half. In addition to these data readouts, we are currently initiating a Phase II efficacy study for NBI-770, the oral NMDA and ought to be negative allosteric modulator as a potential treatment for major depressive disorder. In the early stage pipeline, we have made remarkable progress over the recent months with 5 new programs entering Phase I development. 4 of these programs target the muscarinic system and together with NBI-568, we believe this represents the broadest and deepest muscarinic pipeline of any company in our industry. These Phase I molecules provide the opportunity to explore the potential value of differentiated selective agonism at M1 and M4 receptors, while always excluding agonism at M2 and M3. We have the tools to differentiate these molecules in early clinical development, and thus determine which neurological and psychiatric disorders might best benefit from this differentiated selectivity.

You may begin the year Neurocrine pipeline is broad and diversified as it has ever been and our 32 year history.

Importantly, 2024 marks a catalyst rich year.

Phase II pipeline features several data readouts this year, all of which remain on track for delivery.

<unk> for major depressive disorder with data in the first half.

<unk> the D O inhibitor for cognitive impairment associated with schizophrenia in the second half.

N B 568, and also Derrick and full agonist the treatment of psychosis and schizophrenia also reading out in the second half.

In addition to these data Readouts. We are currently initiating a phase II efficacy study for <unk> 770, the oral NMDA and ought to be negative allosteric modulator as a potential treatment for major depressive disorder.

In the early stage pipeline, we have made remarkable progress over the recent months with five new programs entering phase one development.

Four of these programs target the muscarinic system and together with MDI 506, eight we believe this represents the broadest and deepest muscarinic pipeline of any company in our industry.

Phase one molecules provide the opportunity to explore the potential value of differentiated selective agonism at M. One and M. <unk> receptors, while always excluding agonism at <unk> three.

We have the tools to differentiate these molecules in early clinical development, and thus determine which neurological and psychiatric disorders. My best benefit from this definitely differentiated cell activity.

Eiry W. Roberts: In addition, our Phase I muscarinic portfolio includes an internally discovered selective M4 antagonist, NBI-986 targets for the treatment of movement disorders. The final new entry in our Phase I portfolio is NBI-890, a next generation VMAT2 inhibitor targeting a broad range of potential neurological and neuropsychiatric diseases. I'm extremely proud and enthusiastic about the prospects of today's clinical pipeline and look forward to continuing to partner closely with Jude and his outstanding research and preclinical development team to bring the next generation of innovative, small and large molecules from research into the clinic over the coming years. I'll end here and hand it back to Kevin. Kevin?

The final new entry in our phase one portfolio is <unk> 8090, <unk>. Our next generation <unk> two inhibitor targeting a broad range of potential neurological and neuropsychiatric diseases.

I'm extremely proud and enthusiastic about the prospects of today's clinical pipeline and look forward to continuing to partner closely with Jude and his outstanding research and preclinical development team to bring the next generation of innovative small and large molecules from research into the clinic over the coming years.

Alan here and hand, it back to Kevin Kevin.

Kevin C. Gorman: Thank you, Eiry. So, we've gone a little longer this morning with our opening remarks, mainly due to the fact that there was a lot that we ended last year on - and there is a lot going on here this year. So, we're going to do our best to get through as many of your questions as possible before the top of the hour. So, operator could we open it up for the first question? Yes, as a reminder, if you would like to ask a question. Please press star one on your telephone keypad, you may remove yourself from the queue at any time by pressing star two.

So we're going to do our best to get through as many of your questions as possible before the top of the hour. So operator could we open it up for the first question.

Operator: Yes, as a reminder, if you would like to ask a question, please press star one on your telephone keypad, you may remove yourself from the queue at any time by pressing star two. Our first question will come from Paul Matteis with Stifel. Please go ahead.

Yes, as a reminder, if you would like to ask a question. Please press star one on your telephone keypad, you may remove yourself from the queue at any time by pressing star two.

Our first question will come from Paul Matisse with Stifel. Please go ahead.

Paul Matteis: Hey, good morning. Thanks so much for taking my question, I appreciate it. I wanted to ask about the muscarinic readout coming up in the second half of this year. The study design includes a number of different dose arms. So, I was just curious if you could expand upon how you selected those dose arms and how confident you are that you are in the right range? And then because the study has a number of dose arms and isn't all that bad, are you looking at success in this readout is hitting a P value? Or are we more looking at a dose or two with [inaudible] changes that looks similar to [inaudible] with acceptable safety? Thanks a lot.

Eddie design includes a number of different dose arm. So I was just curious if you could expand upon how you selected those dose arms and how confident you are that you are in the right range and then because the study has a number of dose arms and isn't all that bad are you looking at success. In this readout is hitting a P value are we more looking at a dose or two with Pam changes that.

Similar to <unk> with with acceptable safety. Thanks, so much.

Eiry W. Roberts: Hi, Paul, thanks very much. Thanks for the question. So, this is a dose finding study as you alluded to for NBI-568, and it is an adaptive design that explores several different dose levels. And so, in terms of the sizing and powering of the study, we are more looking for an effect size that is similar to what has been seen before and also potentially a somewhat differentiated tolerability profile. It's not a trial that is powered for individual P values, the different arms there, but it is a reasonable size, large dose finding study with - it will have over 200 patients ultimately and we look forward to reading out in the second half of this year.

Thanks for the question. So this is a dose finding study as you alluded to for <unk>.

<unk> 568, and it is an adaptive design that explore several different dose levels and so in terms of the sizing and powering of the study we are more looking for an effect size that is similar to what has been seen before and also potentially a somewhat differentiated tolerability profile it's not.

A trial that is powered for individual P values the different arms, there, but it is a.

Reasonable size large dose finding study with it we'll have over 200 patients ultimately and we look forward to reading out.

Second half of this year.

Paul Matteis: Okay. Thank you, Eiry.

Operator: Thank you. Our next question will come from Tazeen Ahmad with Bank of America. Please go ahead.

Tazeen Ahmad: Hi, guys. Good morning, thanks for taking my question. Mine's on the chorea launch this year. I wanted to get some more color of what type of contribution you're expecting from that launch or INIGREZZA sales this year, at least directionally. And then, I also wanted to follow up on a comment Eric made in the prepared remarks that I think you said 80% of chorea patients don't receive any therapy today, but you know [inaudible] on the market for several years I was just curious as to why you think they haven't been able to take a bigger share in the years that they've been in the market. Thanks.

Your sense of Korea patients.

<unk> received any therapy today, but you know what.

It has been on the market for several years I was just curious as to why you think they haven't been able to take a bigger share in the years that they've been in the market. Thanks.

Eric Benevich: Yes, good morning. So, I'll take the second question first. What we've seen prior to the launch and then now that we're in the market is that the majority of patients with Huntington's, chorea, either don't get treated at all for their uncontrolled movements or they get treated with an antipsychotic. It may get some partial benefit. Only about 20% of patients with HD chorea get treated with a VMAT2 inhibitor. And you know, what our hallmark of research tell us, what the prescribers tell us is that the deficiencies with the [inaudible] products have led to a fairly high rate of patients not getting treated. Either because of perceptions of complicated dosing and titration, concerns about side effects, or in some cases out of pocket cost. And so, the profile of INGREZZA in Huntington's chorea has a lot of the same attributes as the profile in TD and is the reason that it's the number one, most prescribed VMAT2 inhibitor, in terms of simple dosing, no complex titration, well tolerated. And as I mentioned in my prepared remarks, out of pocket cost is less than $10 for most patients. And so we intend to

So I'll take the second question first.

What we've what we've seen prior to the launch and then now that we're in the market is that the majority of patients with Huntington's chorea.

Neither don't get treated at all for there are uncontrolled movements or.

They get treated with an antipsychotic.

It may get some partial benefit only about 20% of patients with HD create get treated with a <unk> two inhibitor.

And you know what our hallmark of research tell us what the prescribers tell us is that the you know the deficiencies with the tetra vendors and products have led to a fairly high rate of of patients not getting treated.

Either because of perceptions of complicated dosing and titration.

Concerns about side effects or in some cases out of pocket cost.

And so the profile of <unk> in Huntington's Chorea has a lot of the same attributes as the profile in TD and is the reason that it's the number one.

Most prescribed IV met two inhibitor.

In terms of simple dosing no complex titration, well tolerated and as I mentioned in my prepared remarks out of pocket cost is less than $10 for most patients and so we intend to.

Eric Benevich: And so, we intend to grow not only by growing within the VMAT2 treated class, but by expanding the class over time. And to do that we need to encourage more patients and more providers to be treated altogether within that category of HCC. The first part of your question was really around the relative contribution, it's small. And the reason that I say that is that - 2 points: One; we're still just getting off the ground and we're only about a quarter into the launch now. And we're introducing our data to the Huntington's treating community in neurology, but the second reason is that it's a rare disease. It's much smaller patient population, thankfully, than tardive dyskinesia. And so, for every patient with Huntington's chorea there's about 40 patients with TD out there. And ultimately, TD is and will continue to be the main growth driver for our INGREZZA franchise.

Grow not only by.

Hmm.

Growing within the V Matt to treated class, but by expanding the class over time and to do that we need to encourage more patients and more providers to be treated altogether within that category of HCC. The first part of your question was really around the relative contribution is small and the reason that I say that is that too.

One we're still just getting off the ground and we're only about a quarter into the launch now.

And we're introducing our data to the Huntington's treating community in neurology, but the second reason is that it's a rare disease. It's much smaller patient population Thankfully, then tardive dyskinesia and so for every patient with Huntington's chorea.

There's about 40 patients with TD out there and ultimately TD is and will continue to be the main growth driver for Ari Rosa franchise.

Tazeen Ahmad: Okay. Thanks, Eric.

Thank you. Our next question will come from Brian Skorney with Baird. Please go ahead.

Brian P. Skorney: Hey, good morning, everyone and thank you for taking my question. Matt, I was hoping maybe you can help us think about the initial build out of infrastructure for CAH launch and how to think about sort of the SG&A guidance for this year versus what's fully loaded. And then, maybe you can just kind of give us some high level thoughts on what a cadence of launch would look like. Do you see this as a market with high levels of patient awareness and building demand, or is this more of a cadence in patient sort of seeing endocrinologist on a yearly basis and that sort of a point of discussion for a new therapy happening?

Matt I was hoping maybe you can help us think about the initial build out of infrastructure for CA launch and how to think about sort of the SG&A guidance for this year versus whats fully loaded and then maybe you can just kind of give us some high level thoughts on what a cadence of launch would look like do you see this as a market with high levels of patient awareness and building demand or is this more of a cadence.

Patient sort of seeing endocrinologist on a yearly basis and that sort of a point of discussion for a new therapy happening.

Matthew Abernethy: Yeah. So, from a financial perspective, we are going to invest around $50 million this year just to prepare for that launch in 2025. So, from an SG&A perspective, if you look at it holistically for the company showing very nice leverage this year. And even including the $50 million investment. So, Eric can get into the details of the build, but we do expect to have the sales force generally in place by the middle of this year to start educational initiatives and then that will set us up for a launch in 2025. Eric, do you want to comment on the cadence of launch? Yeah as I mentioned in my prepared remarks. 2024 is the year of preparing for the launch but it is also the year of preparing the market for <unk>. And to that end. We're gonna start the process of reaching in educating all the key stakeholders in the CAH community so patients family members and endocrinologists. And part of it is educating them on the nature of the disease. The challenges that <unk> highlighted in her prepared remarks. Our living with CAH on a day to day basis and. The limitations of current treatment with high dose glucocorticoids.

And even including the $50 million investment so Eric can get into the details of the bill, but we do expect to have the sales force generally in place by the middle of this year to start educational initiatives and then that will set us up for a launch in 2025, Eric do you want to comment on the cadence of.

Yeah as I mentioned in my prepared remarks.

Eric Benevich: Yeah, as I mentioned in my prepared remarks. 2024 is the year of preparing for the launch but it is also the year of preparing the market for CRINECERFONT. And to that end, we're gonna start the process of reaching and educating all the key stakeholders in the CAH community. So, patients, family members and endocrinologists. And part of it is educating them on the nature of the disease, the challenges that Eiry highlighted in her prepared remarks of living with CAH on a day-to-day basis and the limitations of current treatment with high dose glucocorticoids. As Matt mentioned, we are in the process of scaling up and hiring a sales force and we're going to deploy that team a few quarters in advance of the anticipated [inaudible] date. And there'll be - getting out there, there'll be doing disease state education, there'll be meeting customers, profiling customers, et cetera, to really set us up for a very strong launch that we expect in 2025.

2024 is the year of preparing for the launch but it is also the year of preparing the market for <unk>.

And to that end.

We're gonna start the process of reaching in educating all the key stakeholders in the CAH community so patients family members and endocrinologists.

And part of it is educating them on the nature of the disease.

The challenges that <unk> highlighted in her prepared remarks.

Our living with CAH on a day to day basis and.

The limitations of current treatment with high dose glucocorticoids.

As Matt mentioned, we are in the process of scaling up and hiring a sales force and we're going to deploy that team a few quarters in advance of the anticipated <unk> date.

And.

There'll be a getting out there there'll be doing disease state education, there'll be meeting customers' profiling customers et cetera to really set us up for a very strong launch that we expect in 2025.

Operator: Thank you. Our next question will come from Phil Nadeau with TD Cowen. Please go ahead.

Phil Nadeau: Good morning. Congratulations on a successful year. A couple of questions for Matt, just based on the 2024 guidance for INGREZZA. First Matt, you mentioned that the gross to net would improve in 2024, can you give us some idea of what the net price you're expecting for INGREZZA is? And then second, on the revenue guidance, the bottom end of the 2024 revenue guide implies only about 5% growth versus the Q4 run rate for INGREZZA. So, we're curious to know a bit more about the patient dynamics that could lead to that relatively modest growth versus the 10% that is assumed at the high end. Thanks.

And then second on the.

The revenue guidance the bottom end of the 2024 revenue guide implies only about 5% growth versus the Q4 run rate for aggressive. So we're curious to know a bit more about the patient dynamics that could lead to that.

Relatively modest growth versus versus the 10% that is assumed at the high end.

Matthew Abernethy: Yeah, and thanks for the question, Phil. Always good to hear from you. As we think about 2024, an overall guidance it really comes down as it does every year to what happens in the first quarter with patient retention and then also new patient generation. So, the guide that we provided today really takes into account what we see today, but we of course are always going to work to try to drive as much on new patient growth as possible throughout the year, and we will of course reassess our guidance when we get to the middle of the year, consistent with past years. From a net price perspective, factoring all the nuts and bolts of price increases and contracting tradeoffs, we would expect the net revenue per script will be somewhere over $5.800 net revenue per script. And just as a reference point to remind you, we did land around $5.600 net revenue per script in 2023.

We think about 2020 for an overall guidance it really comes down as it does every year to what happens in the first quarter with patient retention and then also new patient generation. So the guide that we provided today really takes into account what we see today, but.

But we of course are always going to work to try to drive as much on new patient growth as possible throughout the year and we will of course reassess our guidance when we get to the middle of the year consistent with past years from a net price perspective.

Factoring all the nuts and bolts of price increases and contracting tradeoffs, we would expect the net revenue per script will be somewhere over $5800 net revenue per script and just as a reference point to remind you. We did land around $5600 net revenue per script in 2023.

Phil Nadeau: Very helpful. Thank you.

Operator: Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead.

Thank you. Our next question comes from Brian Abrams with RBC capital markets. Please go ahead.

Brian Abrahams: Hey, guys. Thanks for taking my my question. You mentioned the potential to prepare for an ADCOM for CRINECERFONT. I was wondering if you could maybe speak about what topics you might expect to be discussed there. And I guess, how a potential outcome could tie in to laying the groundwork for payers and any discussions you may be having, as well as furthering the educational efforts that you're going to be initiating this year around the market. Thanks.

As well as furthering the educational efforts that youre going to be initiating this year around the market. Thanks.

Eiry W. Roberts: Okay, thanks. So, let me take the second part. First I mean, in terms of the educational efforts, I think it's really important given the fact that CRINECERFONT will be the first potential medication to come forward into this space in the last sort of 60 to 70 years. [inaudible] we have a - obviously, a group of experts who are incredibly familiar with the current options that they have available for helping this patient population. The opportunity to fundamentally change the paradigm of treating this disease I think is one that's going to require us to engage heavily in educating clinicians, educating the patient population, [inaudible] and everyone else around those patients. So, we will be - we are investing heavily in that already, both on the medical side on the commercial side, obviously in a compliant way ahead of our hopeful approval. With respect to the question around the ADCOM, I mean, the reason we talk about an ADCOM is just because of what I said earlier, really, there hasnt been a medication in this space for so many years. And in addition to that, obviously, it may be an opportunity for the FDA to engage with wxperts in the field outside of those that have worked on the program. We don't have any particular reason to believe that an ADCOM would be necessary, based on our data. We are incredibly impressed with the data that we were able to generate from our Phase III program. I believe that our NDA will be very clear articulate both the benefit and tolerability of CRINECERFONT. And so, we don't have particular topics we're thinking about, it is just in order to be prepared for obviously, making sure that that's in place and in the event that the FDA decides to go down that route.

Potential medication to come forward into this space in the last set of 60 70 years.

Last we have a obviously a group of experts who are incredibly familiar with the current options that they have available for helping this patient population.

That the opportunity to fundamentally change the paradigm of treating this disease I think is one that's going to require us to engage heavily in educating clinicians educating the patient population.

Ladies and everyone else around those patients.

So we will be.

We are investing heavily in that already and both on the medical side on the commercial side, obviously in a compliant way ahead of our hopeful approval.

Speaker Change: With respect to the question around the outcome I mean, the reason we talk about an AD com is just because of what I said earlier really there hasnt been a medication in this space.

For so many years and in addition to that obviously it may be an opportunity for the FDA to engage with.

Experts in the field outside of those that have worked on the program. We don't have any particular reason to believe that an outcome would be necessary based on our data. We are incredibly impressed with the data that we were able to generate a phase III program and believe that our NDA will be very clear.

Articulate both the benefit and Tolerability of connect default and so we don't have particular topics. We're thinking about it is just in order to be prepared for obviously.

Making sure that that's in place and in the event that the FDA decides to go down that route.

Brian Abrahams: Thanks, Eiry.

Operator: Thank you. Our next question comes from Chris Shibutani with Goldman Sachs. Please go ahead.

Unknown: Hey, [inaudible] this is Steven on for Chris. Thanks for taking our question. I think Eric mentioned in the prepared remarks that you expect growth from all three channels of your commercial organization, [inaudible] INGREZZA this year. So, I'm just curious if you can speak about development and progress points you made in the long term care channel and how meaningful we should expect revenues from that channel to be in 2024. Thank you.

Expect revenues from that channel to be in 2024. Thank you.

Eric Benevich: Yeah. So, all three segments of our business are growing nicely, as I mentioned. [inaudible] continues to drive the majority of the opportunity because thats, where the majority of the patients are being cared for with TD. Neurology and LTC are also doing quite well, and at this point, the contribution from each is pretty similar, in terms of our overall business. So, LTC is the newest segment, as I've mentioned before, it's probably the least developed segment because we really haven't been in there as long educating the stakeholders, driving screening diagnosis and treatment. And it continues to really be growing nicely. And so, in such a short period of time for it to be contributing to that level, I think it's a testament to the investments that we made and we're quite happy with the results.

<unk> of our business are growing nicely as I mentioned.

<unk> continues to drive the majority of the opportunity because thats, where the majority of the patients are being cared for with TD.

<unk> and LTC are also doing quite well.

And at this point of the contribution from each is pretty similar in terms of our overall business. So.

LTC is the newest segment as I've mentioned before it's probably the least developed segment.

We really haven't been in there as long.

Educating the stakeholders driving screening diagnosis and treatment.

Harry: And it continues to.

To really be growing nicely and so in such a short period of time for it to be contributing.

Contributing to that level I think it's a testament to the investments that we made and we're quite happy with the results.

Unknown: Alright, thank you.

Operator: Thank you. Our next question comes from Josh Schimmer with Cantor. Please go ahead.

Josh Schimmer: Thanks for taking my questions. Just a couple of quick ones. First; are you seeing any shifts in market share as a result of the once per day AUSTEDO launch? And then, I noticed you've added - [inaudible] I'm pronouncing that correctly, that the pipeline I think in the past you've indicated that might be a product [inaudible] for market building and establishing a sales force, as opposed to generating meaningful revenue. Are you starting to shift that perspective at all? Thank you.

If I'm pronouncing that correctly that the pipeline I think in the past you've indicated that might be a product tanker.

For market building.

Establishing a sales force as opposed to generating meaningful revenue.

Turning to ship that perspective at all thank you.

Eric Benevich: Yes, I'll take your first question. So, the answer is no, we haven't seen any change in market share. It appears to us that deutetrabenazine XR is cannibalizing deutetrabenazine, in terms of their overall business. So, it's more of a shift within that deutetrabenazine franchise than any kind of share gain. The other thing that I'll say is that we didn't see a change of market share in 2023, and we don't expect to see any kind of change in market share, at least any kind of negative change in market share in 2024.

So the answer is no we haven't seen any change in market share.

It appears to us that.

That do Tetra benzene XR.

Is cannibalizing do tetra benzene and.

In terms of their overall business. So it's more of a shift.

Within within that do Tetra bendamustine franchise than any kind of share gain the other thing that I'll say is that we didn't see a change of market share in 2023, and we don't expect to see any kind of change in market share or at least any kind of negative change in market share in 2024.

Matthew Abernethy: Yeah, the only thing that I'd add, Eric, is that the market itself has just been incredibly rich. There's so many patients that need help with their tardive dyskinesia in great unmet need. So, when you look at what we were able to achieve this year, record year-over-year growth, over $400 million. And I would just say from a class perspective, this continues to be a great opportunity and looking forward to helping more patients who need help with their tardive dyskinesia. Eiry, do you want to comment on the [inaudible]? yes, Sidney So F. Modi is a steroid treatment that is currently approved in the in Europe for the treatment of CAH in adults and. And as such I think it is. Essentially has some complementarity to connect the funds. We are in the U S. We do not have an approval for <unk>. Currently we are reading out two trials of <unk> in the <unk>. First half of this year and based on the data from the two phase II trials, obviously, we'll update you as to what our next time zone.

This continues to be a great opportunity and looking forward to helping more patients who need help with their tardive dyskinesia.

Do you want to comment on the Modi, yes, Sidney So F. Modi is a steroid treatment that is currently approved in the in Europe for the treatment of CAH in adults and.

Eiry W. Roberts: Yes, certainly. So, EFMODY is a steroid treatment that is currently approved in Europe for the treatment of CAH in adults. And as such, I think it essentially has some complementarity to CRINECERFONT. In the U.S. we do not have an approval for EFMODY currently, we are reading out two trials of EFMODY in the first half of this year, and based on the data from the two Phase II trials, obviously, we'll update you as to what our next plans are.

And as such I think it is.

Essentially has some complementarity to connect the funds.

We are in the U S. We do not have an approval for <unk>. Currently we are reading out two trials of <unk> in the <unk>.

First half of this year and based on the data from the two phase II trials, obviously, we'll update you as to what our next time zone.

Josh Schimmer: Okay.

Operator: Thank you. Our next question comes from Anupam Rama with JP Morgan. Please go ahead.

Anupam Rama: Hey, guys. Thanks, so much for taking the question. Just maybe a quick pipeline question, so, the AMPA potentiator in MDD, that's one of the next catalyst expected in the first half of 2024. Maybe you could describe the study, the key endpoints, and what you're looking for in this program to give you confidence to move some of that space.

Just maybe a quick pipeline question, so the amp up potentiate or an M D D.

One of the next catalyst expected in the first half of 'twenty four maybe you could describe the study the key endpoints and what Youre looking for in this program to give you confidence to move some of that space.

Eiry W. Roberts: Thanks, Anupam. So, yes, you're right. The first half of this year we will read out the data from NBI-845 which is a potentiator as a potential treatment for major depressive disorder. This is a dose finding study, compares two different dose levels of AMPA potentiators to placebo, using a pretty standard, primary endpoint of the [inaudible] at week 4. And the goals here with this mechanism of action, obviously, since it potentially ketamine like, yet through a downstream mechanism associated with NMDA is that we actually would see a more rapid answer of antidepressant activity than is seen usually with SSRIs and other treatment. So, we are looking at [inaudible] the primary endpoint, but we have multiple other secondary endpoints within this dose finding study, which allows us to look at function and quality of life, as well as at the other psychiatric endpoints. And so in essence, we will be looking at the totality of the information coming out of this dose finding study to make a decision as to whether to proceed.

The first half of this year, we will read out the data from MBIA four five which is a.

Potentiate that.

As a potential treatment for major depressive disorder. This is a dose finding study compares two different dose levels of.

Potentiate it to placebo using a pretty standard primary endpoint of the mattress score at week, four and Nicola here with this mechanism of action, obviously since it potentially ketamine like.

Yet.

Josh Schimmer: And in those through a downstream mechanism associated with NMDA is that we actually that would see a more rapid onset antidepressant activity than is seen usually with ssris and other treatment. So.

So we are looking at mattresses, the primary endpoint, but we have multiple other secondary endpoints within this dose finding study, which allows us to look at.

Josh Schimmer: Function and quality of life as well as at the.

The other psychiatric endpoints and so in essence, we will be looking at the totality of the information coming out of this dose finding study to make a decision as to whether to proceed.

Anupam Rama: Thanks so much for taking my question.

Operator: Thank you. Our next question comes from Carter Gould with Barclays. Please go ahead.

Carter Lewis Gould: Good morning. Thanks for taking the question. Maybe another one for Eiry. It was brought up a little bit at the analyst day, but frankly kind of got overshadowed by some of the other updates and that is sort of the next generation of VMAT2 inhibitors, can you just talk about, obviously, the ATS study that is ongoing and you've talked a little bit about how that will - the impact of that. Could you just maybe lay out kind of your expectations and sort of the progress you expect on the broader effort on VMAP2 follow ons, over the course of the next 12 to 18 months.

It was brought up a little bit at the analyst day, but frankly kind of got overshadowed by some of the other updates and that is sort of the next generation of.

<unk> two inhibitors can you just talk about obviously the Ats study is ongoing and you've talked a little bit about how that will the.

The impact of that could you just maybe lay out kind of your expectations and sort of the progress you expect on the on sort of the.

This broader effort on if you're about to follow ons over the course of the next 12 to 18 months.

Eiry W. Roberts: Yeah. So, we are just entering the clinic with NBI-890, which is the VMAT2 follow on, and obviously, given the depth of knowledge that we have of this VMAT2 mechanism, this is a really important mechanism and platform for us. And valbenzene is an amazing medication in terms of its profile that Eric alluded to earlier. And so, we have had to keep the bar really high in terms of the ability to differentiate these next generation molecules coming into the clinic. And so, we haven't talked too much about the profile of the VMAT2 inhibitors yet, we will obviously do that as we generate Phase I data. But we would seek to differentiate with this molecule, both in terms of potential indications that we will go into, but also, in some of the characteristics of the molecule itself that might lend itself for other areas, such as long acting intramuscular injection or other approaches that are important in the neuropsychiatric arena.

The mechanism and a platform for us.

And Val benzene is an amazing medication in terms of its profile that Eric alluded to earlier and so we have had to keep the bar really high in terms of the ability to differentiate with next generation molecules coming into the clinic.

And so we haven't talked too much about the profile of the FEMA two inhibitors. Yeah. We will obviously do that as we generate phase one data.

But we would seek to differentiate with this molecule both in terms of potential indications that we will go into but also in some of the characteristics of the molecule itself that might lend itself for other areas such as long acting intramuscular injection or other approaches that are important in the neuropsychiatric arena.

Speaker Change:

Okay.

Operator: Thank you. We'll take our next question from a [inaudible] with Jefferies. Please go ahead.

Unknown: Good morning, thanks for taking our question. This is [inaudible]. On the Phase II schizophrenia trial for for M4 agonist, 568, that is going to be reading out this year. It sounds like you are prioritizing safety over efficacy. How much how much efficacy are you going to maybe give up here, in comparison to other competitors, like [inaudible] order to move forward into a Phase III study? Thanks.

Phase II schizophrenia trial for EMCORE agonist 568.

That will be reading out this year. It sounds like you are prioritizing safety over ask see homeless SEIU, allowing for maybe gave up here in comparison to other competitors like <unk> in order to move forward into a phase III study. Thanks.

Eiry W. Roberts: Thank you. So, the NDI-568 molecule is a highly selective, M4 agonist. And as such, I think we know now from both [inaudible] and the cerebellum molecules that the M4 mechanism is implicated in the psychosis and schizophrenia and blocking - and agonizing M4 can result in benefit, in terms of improvements of the [inaudible] and psychosis symptoms. Clearly there is a differentiation between the molecules in terms of the way in which they agonize M4. And so, that may play out in terms of differentiation efficacy, but it also may play out in terms of differentiated tolerability. And so, I wouldn't say that we are only interested in tolerability, we're interested in both. This is a dose finding study and as part of that we will be able to look at the efficacy in terms of the impact on psychosis scores, and the tolerability, in terms of overall tolerability to this molecule. So, I think both are important and it'll be an integration of those data from the Phase II readouts that will be important in determining a path forward.

So the MDI 568 molecule is a highly selective and full agonist and as such I think we know now.

Both car T and the cerebellum molecules that the end full mechanism is implicated in the psychosis and schizophrenia and blocking and agonizing in for Ken results and benefit intense the improvements the patents scores and psychosis symptoms.

Clearly there is a different and differentiation between the molecules in terms of the way in which they agonize.

And so and so.

Speaker Change: So that may play out in terms of differentiation efficacy, but it also may play out in terms of differentiated tolerability and so I wouldn't say that we are only interested in tolerability. We're interested in boats. This is a dose finding study and as part of that we will be able to look at the efficacy in terms of the impact on psychosis scores and the.

Tolerability in terms of overall colored.

Tolerability to this molecule. So I think both are important and it'll be an integration of those data from the phase II readouts that will be important in determining a path forward.

Oh.

Operator: Thank you. Our next question comes from Jay Olson with Oppenheimer. Please go ahead.

Jay Olson: Congrats on all the progress and thanks for taking the question. Just going back to CRINECERFONT, can you talk about how long patients need to be treated with CRINECERFONT before they start to experience some of the benefits on the complications of CAH? Like cardiovascular, bone density. And do you think you'll have some of that data when you file? And then separately, do you have any plans to study CRINECERFONT in other diseases besides CAH? Thank you.

Just going back to connect their front can you talk about how long patients need to be treated with <unk> before they start to experience some of the benefits on the complications of CAH like cardiovascular bone density and do you think you'll have some of that data when you file and then.

And separately do you have any plans to study chronister font and other diseases. Besides CAH. Thank you.

Eiry W. Roberts: That’s a lot of questions there. Taking them one at a time, in terms of the effectiveness of CRINECERFONT and its direct benefit in terms of the androgen control, just to make a comment there, we see that very rapidly, and we’ve shown that on two occasions, first in our Phase II proof-of-concept study where within 14 days of dosing, the degree of reduction in androgen control - of androgens was pretty much maximal, because that was also how it played out in the four-week study in our Phase III data. In terms of controlling androgens, CRINECERFONT does that very rapidly. Obviously, that then allows clinicians to reduce the steroid dosing, and by both controlling androgens with CRINECERFONT and being able to reduce steroid dosing, that’s how we get to the benefit associated with the clinical longer term outcomes. We do have measures of clinical outcome in terms of metabolic measures, bone related measures, growth and other important elements within our NDA submission. Obviously, those are brd on data out to one year, essentially, and beyond that, the other impressive thing about the program to date has been the rollover rate into the open label, which is essentially greater than 95% for both the adult and pediatric trials, and so we are collecting longer term open label data on an ongoing basis, and we’ll continue to do that until we reach the market. Also, we have a registry effort going on, called catalog, which will allow us to put in context our clinical outcome data in terms of what is seen in the general population of CAH.

Benefit intensive the androgen control.

Just to make a comment that we see that very rapidly and we've shown that on two occasions.

First in our phase II proof of concept study win within 14 days of dosing.

The degree of a reduction in androgen control of androgens was pretty much maximal because not all adults. So how it played out in the full week our study in our phase III data so in terms of controlling androgens.

Speaker Change: That very rapidly obviously that then allows clinicians to reduce the steroid dosing and by both controlling androgens with tenacity and being able to reduce steroid dosing. That's how we get the benefit associated with the clinical longer term outcomes.

Do have measures of clinical outcome in terms of metabolic measures bone related measures growth and other important elements within our NDA submission. Obviously those are based on data out to one year essentially and beyond that the other impressive thing about the program to date has been the rollover rates in.

Two the open label.

Is it essentially greater than 95% for both the adult and pediatric trials and so we are collecting longer term open label data on an ongoing basis and we'll continue to do that until we reach the market.

Also we have a a legend.

Registry ethic going on cold catalog, which will allow us to put in context, all clinical outcome data intense in terms of what is seen in the general population of CAH.

Jay Olson: Great, Thank you. And any plans for other diseases?

Great. Thank you and any plans for other diseases.

Eiry W. Roberts: Oh, actually I think - obviously, we are thinking about that on an ongoing basis. I think Jude also alluded to it at our R&D day that we have a whole effort around next-generation molecules in CAH and other indications in that space as well, and so we’ll certainly be talking more about that in due course.

I think Jude also alluded to at the R&D day that we have a whole effort around next generation molecules in CAH and other indications in that space as well and so we'll certainly be talking more about that in due course.

Jay Olson: Great. Thank you very much.

Operator: Thank you. Our next question comes from Marc Goodman with Leerink. Please go ahead.

Unknown: Hey, this is Rudy on the line for Marc. Thanks for taking my question. Can you talk about your IP following the recent patent litigation settlement, and just curious what are your current thoughts on impact of IRA on your pricing towards the end of this decade. Thank you.

So can you talk about your IP barring the recent patent litigation settlement and just curious what are your current sales.

On the impact of IRI.

On your pricing towards the end of this decade. Thank you.

Eric Benevich: We’re very pleased with the way that the litigation ended up. We have protection that goes out into 2038 at this point in time, so I think that that really spoke to the impressive patent efforts that we put behind all of our molecules here at Neurocrine. When it comes to the IRA, as you know, the first 10 drugs are under negotiation right now. In September of this year, we’re going to see the first time what those negotiations yielded, so I think we all look forward to seeing that before we can comment any further on what we think the IRA impacts are going to be.

The litigation ended up we have.

Protection that goes out into 'twenty 38 at this point in time, so I think that.

That really spoke to the <unk>.

Impressive patent efforts that we put behind all of our molecules here at.

Marc Goodman: At Neurocrine when it comes to the IRR as you know the first 10 drugs are under negotiation right now at in September of this year, we're going to see.

Marc Goodman: The first time, what those negotiations yield and so I think we all look forward to seeing that before we.

We can comment any further on what we think the.

Marc Goodman: The impacts are going to be.

Unknown: Got it. Thank you.

Thank you.

Operator: Thank you. Our next question comes from Myles Minter with William Blair. Please go ahead.

Myles Minter: Hi, congrats on the progress. Thanks for the question. Just a quick one on the Phase I 570 trial, the dual M1, M4 agonist in healthy volunteers, I think that trial initiated in September. Just wondering how dosing is going for that and when we’ll hear about safety for that program. Secondly, would you ever think about running head-to-head studies against 568 or 569 in a CNS indication? Thanks.

Just a quick one on the finance fund five Stephanie Shaw the dual <unk> agonist in healthy volunteers trial initiated in September just wondering have Darcy and his guidance for that and when we'll hear about safety for that program.

And secondly would you ever think about running head to head studies against fast excited phosphatase non CNS indications. Thanks.

Eiry W. Roberts: Thanks Myles. On the 570, that’s progressing very well. We are going through the Phase I program and at some point, obviously, we’ll come forward and talk about that more as we enter Phase II - that’s usually what we tend to do in that space, but things are progressing as expected. You know, there’s always a lot of discussion about whether to try to put more than one investigational product into a clinical trial, in order to profile them directly with one another. As you can imagine, that is something we’ve talked about in the context of the fact that we have such a broad portfolio of muscarinics. It’s very challenging to do that, though, given the fact that we want to try to accelerate each molecule as much as possible individually, and so at least in my experience over many years in this business, they don’t seem to line up perfectly for you to be able to do that. In the absence of being able to do that, what we are doing is essentially running very, very similar Phase I programs for each of these assets, so that we can look at the same measures, look at the same outcomes, and understand how to compare those individual molecules indirectly.

On the $5 70 that is progressing very well and we are going through the phase one program and at some point, obviously will come forward and talk about that more as we enter phase two that's usually what we tend to do in that space, but things are progressing as expected.

And you know there's always a lot of discussion about whether to try to put more than one investigational products into a clinical trial in order to profile them directly with one another as you can imagine that is something we've talked about in the context of the.

The fact that we have such a broad portfolio of muscarinic.

It's very challenging to do that though given the fact that we want to try to accelerate each molecule as much as possible.

Individually and so at least in my experience over many years in this business. They don't seem to line up perfectly for you to be able to do that.

And so.

In the absence of being doing and being able to do that what we are doing is essentially running very very similar phase one program for each of these assets. So that we can look at the same measures look at the same outcomes and understand how to compare those individual molecules indirectly.

Myles Minter: Fair enough. Thanks, Eiry.

Operator: Thank you. Our next question comes from Neena Bitritto-Garg with Deutsche Bank. Please go ahead.

Neena Bitritto-Garg: Hey guys, thanks for taking my question. I just wanted to circle back to the M4 read-out later this year and Paul’s question originally about dosing. Is there anything else that you can kind of share on the dose levels that you’re testing and dosing frequency, and maybe how they may compare to some of the doses that we’ve seen for emraclidine and KarXT from an activity perspective? Thanks so much.

Neena Bitritto: And maybe how they may compare some of the doses that we've seen for Iraq with in car T from an activity perspective. Thanks, so much.

Eiry W. Roberts: We haven’t shared the doses from our Phase II dose finding study up to this point. Obviously it’s not that long before we get our data, so we’ll get to see that later this year. What I can say is that we’re confident on the dose range that we’re testing, brd on an integration of our preclinical data, both efficacy and tolerability from the toxicology program, and also from our Phase I studies where obviously we explored a lot of different pharmacology to understand how to pick the right doses for Phase II.

Phase two dose finding study up to this point, obviously, it's not that long before we get our data. So we will get to see that later this year.

What I can say is that we're confident on the dose range that were testing based on an integration of our preclinical data both efficacy and Tolerability from the toxicology program and also from our Phase One studies, where obviously, we explored a lot of different pharmacology to understand how to pick the right doses for phase two.

Neena Bitritto-Garg: Got it, thank you.

Got it thank you.

Operator: Thank you. Our next question comes from Jeffrey Hung with Morgan Stanley. Please go ahead.

Unknown: Hi, this is Michael [inaudible] on for Jeff Hung. Thank you for taking our questions. Could you talk a little bit more about EFMODY? What are you hoping to see in the Phase II data, and how would you see this becoming part of the treatment paradigm? Is there anything to suggest maybe different uptake, depending on whether a patient is in early adolescence versus adulthood? Thank you.

Would you talk a little bit more about if modi what are you hoping to see in the phase II data and how would you see this becoming part of the treatment paradigm is there anything to suggest maybe different uptake depending on whether a patient is in early adolescence versus adulthood.

Neena Bitritto: <unk>.

Eiry W. Roberts: Yes, we really haven’t talked much about the EFMODY strategy particularly here in the U.S. As I said, it is an approved product in Europe for CAH, and these are just very straightforward Phase II read-out studies. Once we have the data, I’m sure we’ll talk a little bit more about that and whatever our next steps might be.

And these are just very straightforward phase II readout studies once we have the data I'm sure, we'll talk a little bit more about that in the end.

Whatever next steps might be.

Unknown: Thank you.

Operator: Thank you. Our next question comes from Danielle Brill with Raymond James. Please go ahead.

Danielle Catherine Brill: Good morning. Thank you so much for the questions. I guess I’d like an update on the cerebral palsy dyskinesia and schizophrenia studies of valbenazine. Should we expect data from those studies this year? And then, what sort of impact to sales might we expect from the sprinkle powder formulation of INGREZZA, once it’s approved? Thanks so much.

I'd like an update on Mr. <unk>, our policy dyskinesia in schizophrenia studies in valves benzene should we expect data from that study. This year and then what sort of impact to sales might we expect Banco powder formulation of the congrats that once its approved thanks so much.

Eiry W. Roberts: I can give an update on the ATS and DCP programs. Both are enrolling and we anticipate data during next year.

Eric Benevich: Yes, and just a quick comment on the sprinkle formulation - obviously it’s not an approved formulation, but we’re looking forward to, upon approval, rolling it out. We estimate that 5% to 10% of patients with either Huntington’s chorea or tardive dyskinesia experience difficulty in swallowing, so this may be a better alternative for them, and so we’re looking forward to introducing that product upon approval.

Yes, and just a quick comment on the sprinkle formulation obviously.

It's not.

Proved formulation, but we're looking forward to upon approval rolling it out we estimate that 5% to 10% of patients with either Huntington's chorea or tardive dyskinesia extreme difficulty in swallowing. So this may be a better alternative for them.

Speaker Change: And so we're looking forward to introducing that product upon approval.

Operator: Thank you. Our next question comes from Laura Chico with Wedbush Securities. Please go ahead.

Laura Chico: Hey, good morning guys. Thanks for taking the question. Obviously a lot of discussion today on your internal pipeline activities, but wondering if you can discuss your appetite for external BD at this point, and what flexibility does the balance sheet now provide in terms of potential deal size? Thank you.

Kyle Gano: Hey, this is Kyle. Thanks for the question this morning. I think what you’ve seen here from Neurocrine over the past year was good progress on bringing programs from our internal drug discovery efforts into the clinic - we put five programs in last year. Our team, we work with great urgency here in business development. We don’t feel like we have the need to do something large at this particular time. I think what we would expect here over the near term, midterm is to continue to help our research team accelerate some of their efforts and bring their assets that they’re currently working into the pipeline, to help us transform that pipeline that we’ve been discussing at our R&D day into this next year. In terms of what we’re looking at beyond helping our research colleagues, we’re probably not going to spend a lot of time looking at things that are pre-proof of concept, so it’s earlier stage opportunities to bring in technologies for our research team, and then obviously anything that’s a de-risked, later stage clinical stage asset through commercial are things that would be of interest to us. They are few and far between, as you know, and they are quite expensive as well, so we’d look at those but I think our mind right now is doing what we can to help build the pipeline organically.

Our team worked with great urgency here and business development, but we don't feel like we have the need to do something larger this particular time I think.

We would expect here over the near term mid term is to continue to help our research team accelerate some other efforts and bring.

They're assets that they are currently working on in the pipeline to help us.

Transform that pipeline that we've been discussing.

At our R&D day in to this next year.

So in terms of what we're looking at beyond helping our research colleagues, we're probably not going to spend a lot of time looking at things that are pre proof of concept. So its earlier stage opportunities to bring in technologies for our research team and then obviously anything that's a derisked later stage clinical stage asset through commercial.

Speaker Change: Things that would be of interest to us there are few and far between as you know and they are quite expensive that well. So we look at those but I think our mind right now.

Then what we can to help build the pipeline organically.

Matthew Abernethy: When you think about how we expect to drive shareholder value, you can see where our money’s going - to continue to drive growth in INGREZZA, getting ready to launch CRINECERFONT - I think that’s going to be a meaningful contributor to both help patients and then also to Neurocrine’s top line, and a lot of investment in our internal research programs. Between all the Phase I starts that we have this year, as well as what Jude highlighted at R&D day, we feel very confident about what we have going forward. We of course have financial flexibility with $1.7 billion in cash, and then also a growing EBITDA profile. We do have the financial flexibility, but right not we’re really prioritizing executing what we have, and we have a lot to look forward to.

Shareholder value you can see where money is going to continue to drive growth in <unk> getting ready to.

Speaker Change: Launch Carnesi fun, and I think thats going to be a meaningful contributor to both help patients and then also two trends.

Top line and a lot of investment in our internal research programs between all the phase one starts that we have this year as well as what Jude highlighted at R&D day, we feel very confident about what we have going forward. We of course have financial flexibility with $1 7 billion in cash and then also growing.

EBITDA profile, we do have the financial flexibility, but right now we are really prioritizing executing what we have been.

We have a lot to look forward to.

Laura Chico: Thank you.

Operator: Thank you. Our next question comes from Sumant Kulkarni with Canaccord Genuity. Please go ahead.

Sumant Kulkarni: Morning, thanks for taking my question. On your efforts in major depressive disorder, do you think there is any medicine approaching that indication within episodic versus chronic treatment, and do you expect either 770 or 845 to have an episodic component or a more durable efficacy aspect to [inaudible]?

Expected adventure dosing.

Eiry W. Roberts: I think the goal with our current efforts in both 985 and also 770 is to be able to try to replicate some of the findings that have been seen with ketamine, but to do it in a way that expands on the efficacy that obviously you’ve been seeing in that area. Episodic dosing is the part of the consideration there, and we haven’t talked very much about our dosing regimen for our current programs. We have said for 770, this is an oral approach to NR2B NAM - that is the first, to our knowledge, oral approach to this target, and obviously as we endeavor to generate the data from those Phase II studies, we’ll be able to talk more about the plans moving forward.

And 98, five and also 770 is to be able to try to replicate.

Speaker Change: Some of the findings that have been seen with ketamine.

But to do it in a way that is.

It expands on the efficacy that overhang has been seen in that area.

And so episodic dosing as a part of the consideration that we haven't talked very much about dosing regimen. So that our current programs. We have set for 770 <unk>. This is an oral approach to and ought to be none of that is the first to our knowledge oral approach to this target.

Obviously as we.

Speaker Change: Endeavour to generate the data from this phase two studies, we'll be able to talk more about the plans moving forward.

Sumant Kulkarni: Thank you.

Operator: Thank you. Our next question comes from Evan Siegerman with BMO Capital Markets. Please go ahead.

Unknown: Hi guys, [inaudible] on for Evan. Thanks for taking our question. Coming back to the muscarinics, you’re using an M4 agonism in the Phase II for schizophrenia, but the antagonism for the Phase I in treatment of movement disorders. Maybe can you walk us through the mechanism of action differences and what gives you confidence for those indications, and expectations for how antagonism can be differentiated for movement disorders. Thank you.

Thanks for taking our question coming back to the muscarinic youre using an M. Four agonism in the phase two for schizophrenia, but antagonism for.

The phase one to treat movement disorders are maybe can you walk us through the mechanism of action differences and what gives you confidence for those indications and expectations for <unk> antagonism can be a differentiator for movement disorders.

Eiry W. Roberts: The approaches here are very different. M4 agonism, we are focused on looking at that in the context of treating neuropsychiatric disorders, particularly schizophrenia as the starting indication, and it’s very clear, I think now from data generated in this field, that the M4 system plays a role in the psychosis within schizophrenia. For the M4 antagonist, we’re actually targeting movement disorders, and so in terms of the M4 systems that are associated with abnormal movement within the brain, in diseases such as Parkinson’s tremors, dystonia, that is disrupted, and antagonizing this system, we believe has the potential to add value and to be able to treat those disorders, so it is very different in terms of the approach that we’re taking there.

So the approaches here a very different ample agonism, we're focused on looking at that in the context of treating neuropsychiatric disorders, particularly schizophrenia, starting indication and it's very clear I think now from data generated in this field that.

For system.

Speaker Change: Plays a role in the psychosis within schizophrenia.

Speaker Change: For the M. Four antagonist, we're actually targeting movement disorders and so.

In terms of.

And for systems that are associated with the normal movement within the brain in diseases, such as Parkinson's dystonia.

Speaker Change: Dystonia.

Speaker Change: That is disrupted and.

<unk> bees. This system, we believe has the potential to add value and to be able to treat those disorders. So it is very different in terms of the approach that we're taking there.

Okay.

Thank you. Thank you. Thank you we will take our next question from David Wong with Citigroup. Please go ahead.

Unknown: Thank you.

Operator: Thank you. We’ll take our next question from David Hoang at Citigroup. Please go ahead.

David Hoang: Hi, thanks so much for taking the question. Maybe just to circle back on INGREZZA for a moment, could you talk a little bit about the higher end of the guidance range in 2024, what would be the factors that would play into that, and maybe along those lines, in terms of accessing the remaining two-thirds of undiagnosed TD patients, do you perceive any barriers to reaching that group?

Maybe just to circle back on <unk> for a moment.

Could you talk a little bit about.

The higher end of the guidance range in 2024, what would be the factors that would play into that in.

And maybe along those lines.

In terms of accessing the remaining two thirds of undiagnosed TD patients do you perceive any you know any barriers to reaching that group.

Eric Benevich: Yes, as we mentioned earlier in terms of the 2024 guidance range, it’s really driven by the success that we’ll have early in the year in driving new patient starts and continuing to retain existing patients. As we get to the later part of the year or middle of the year, as Matt said, we’ll re-assess and tighten up what our expected guidance is. In terms of being able to continue to develop the market, continue to drive recognition, diagnosis and treatment, the fundamentals remain the same. When we started with the launch of INGREZZA over six years ago, only a very small fraction of the TD patients had actually been diagnosed, and none had been treated effectively, so we’ve made great progress. Now, we believe that about a third of all TD patients have been diagnosed and yet only about half of the time are they actually offered treatment with VMAT2 inhibitor, so there is still a lot of room in terms of organic growth and a lot of opportunity to make a big difference in patients’ lives. The fundamentals of what we do, both in terms of educating healthcare providers across psychiatry, neurology and long term care, as well as continuing to invest in long term - or excuse me, in DTC, to reach and educate those that are suffering from TD, and encouraging them to have that conversation with their doctor. These are the things that we’re doing. We’re very focused on education, as Matt said, and we’re continuing to drive leverage within our existing TD and HD franchises.

Yes.

As we mentioned earlier in terms of the 2024 guidance range, it's really.

Driven by.

The success that you know that.

We will have early in the year.

In driving new patient starts and continuing to retain existing patients and as we get to.

Later part of the year or middle of the year as Matt said, we'll reassess and tightened up.

You know what our what our expected guidance says.

In terms of being able to continue to develop the market continue to drive.

Recognition diagnosis and treatment the fundamentals remain the same.

You know that when we started with the launch of <unk> over six years ago, only a very small fraction of the PD patients had actually been diagnosed and that had been treated effectively. So we've made great progress in how we you know we believe that about a third of all TD patients have been diagnosed and yet only about half the time.

Or are they actually offered treatment with a <unk> two inhibitor. So there's there's still a lot of room in terms of organic growth and a lot of opportunity to make a big difference in patients' lives and so the fundamentals of what we do.

Both in terms of educating health care providers across.

Psychiatrists neurology in long term care as well as continuing to invest in long term or excuse me in DTC.

To reach and educate those that are suffering from PD and encouraging them to have that conversation with their doctor. These are the things that we're doing we're very focused on education as Matt said.

Speaker Change: And we're continuing to drive leverage within our existing.

PD and HD franchises.

Operator: Thank you. We’ll take our next question from Mohit Bansal with Wells Fargo. Please go ahead.

Mohit Bansal: Thank you very much for the question. Maybe one question on the expense side. It seems like there is some level of margin improvement here on the SG&A side, but you are committing to spending or investing in R&D. As you go forward, I mean, it’s still close to 40% SG&A as a percent of sales. As you move forward, how should we think about the leverage given that for CAH, you still may have to invest money in terms of that launch preparation? Thank you.

For the question.

Maybe one question on the on the expense side, So I mean.

Seems like there is some level of margin improvement in the SG&A side.

But you are committing to spend.

Spending or investing in R&D.

As you go forward I mean still at close to 40% SG&A as supposed to know says as you move forward how should we think about the leverage.

Given that <unk> may have to invest.

But in terms of in terms of that launch preparation.

Matthew Abernethy: Yes, I think the SG&A leverage, when you take a step back and think about where we were in 2022, we were at 51%. I think this year in 2024, if you exclude CRINECERFONT, we’d be down to 41%, so I think - you know, 1,000 basis points of leverage over two years is quite substantive, and proud of what the team has been able to accomplish with the investments that we’ve made. In terms of leverage going forward, the investment behind CRINECERFONTis not going to be anything near the investment that we have behind INGREZZA. I’d expect it to be very accretive early in the launch, and we’ll of course give updated guidance next year in terms of expense and revenue expectations. But I think the addition of CRINECERFONT is only helpful to our SG&A leverage ambitions over the years ahead.

At 51% I think this year in 2024, if you exclude <unk>, we'd be down to 41%. So I think.

1000 basis points of leverage over two years is quite substantive and proud of what the team has been able to accomplish with the investments that we've made.

In terms of leverage going forward.

Investment behind Kronos or fun it.

Is not going to be anything near the investment that we have behind it.

And Greg I'd expect it to be very accretive.

Early in the launch and we will of course give give updated guidance.

Guidance next year in terms of expense and revenue expectations, but I think the addition of Chronicity of bond is only helpful.

Two our SG&A leverage ambitions over the years.

Yeah.

Mohit Bansal: Excellent. Thank you.

Operator: Your next question comes from Uy Ear from Mizuho. Please go ahead.

Thank you. Our next question comes from Leap year with Mizuho. Please go ahead.

Uy Ear: Hi guys, thanks for taking my question. Matt, I think you said the 4Q INGREZZA number, the growth was offset by gross-to-net. I was wondering if you can help us understand the dynamics of gross-to-net in the quarter, and as well as the factors that will improve gross-to-net in 2024. Thanks.

I was wondering if you can sort of help us understand the dynamics of the gross to net in the quarter and as well as the the.

Factors that will improve gross to net in 2024.

Matthew Abernethy: You know, when you think about our Q4 results, it’s our first quarter ever of $500 million in sales, and we’re quite encouraged by what we saw. There’s always quarterly gyrations in terms of whether it’s timing of orders, timing of patients getting refills, etc., and so there’s choppiness to certain quarters. Q3 was a blowout quarter; Q4 was another great quarter, and I think we feel very good with how we’re positioned, headed into 2024. The gross-to-net dynamic that I commented on is very consistent with what we’ve had in previous years. There’s an accounting requirement where you have to take an incremental discount on your channel inventory, and so that’s something that put pressure on our numbers a bit in Q4. The only other item that I’d call out as it relates to net revenue per script, we didn’t take our price increase until very late in the quarter, and in previous years there was some level of contribution in our Q4 numbers associated with the price increase. The improvement in this year’s net revenue per script comes down to price increases and then the contract decisions that we make, their trade-offs, and I think that overall, that’s what led to an improved net revenue per script, going from $5,600 in 2023 to something over $5,800 in 2024.

Leap year: First quarter ever of $500 million in sales and were quite <unk>.

Encouraged by what we saw there was always a quarterly gyrations in terms of whether it's timing of orders timing of patients getting refills et cetera.

So there's choppiness to certain quarters Q3 was a blowout quarter Q4 was another great quarter and I think we feel very good with how we're positioned.

Discount on your channel inventory and so that's something that put pressure on our numbers a bit in Q4 and the only other item that I would call out as it relates to net revenue prescript, we didn't take a price increase until very late in the quarter and in previous years. There was some level of contribution and her and her team.

Poor numbers associated with the price increase so the improvement in next year's or in this year's net revenue prescript. It comes down to price increases and then the contract decisions that we make.

There are tradeoffs and I think that overall, that's what led to an improved net revenue per script.

Leap year: Going from 5600 in 2020 through to something over 5800.

In 2024.

Yeah.

Uy Ear: Thanks.

Operator: Thank you. Our next question comes from David Amsellem with Piper Sander. Please go ahead.

Unknown: Hi, this is Schuyler on for David. First, any thoughts on the potential pricing of CRINECERFONT and the discussions you’ve been having with payors, and do you expect the reimbursement landscape will be different between adults and pediatrics? Then second, could you provide any updates on the development plan for the M1 preferring agonist, and just talk mechanistically to the value proposition of just targeting M1 versus M4. Thanks.

Scott: And do you expect the reimbursement landscape will be different between adults and pediatrics and then second could you provide any updates on the development plan for the M. One, preferring agonists and just talk Mechanistically to valley.

<unk> proposition of just targeting online versus I'm sorry. Thanks.

Eric Benevich: Yes, so obviously we’re very enthusiastic about the clinical profile that emerged with CRINECERFONT. With regards to pricing, it’s a little bit premature to comment on that, other than to say that this is a rare disease and we would expect to have rare disease pricing. We’ve had initial conversations with payors and I’ve been quite pleased, and maybe a little bit surprised - pleasantly - that they seem to be acutely aware of the issues associated with chronic high dose steroid treatment, and so we’ve got a lot of work to do still in terms of understanding the value that’s emerging from the clinical data. Certainly we believe that the pricing will be in line with the value that we bring to market.

Yes. So obviously you know we're very enthusiastic about the clinical profile that emerged with kronos or font with regards to pricing, it's a little bit premature to comment on that other than to say that this is a rare disease.

And we would expect that to have rare disease pricing, we've had initial conversations with payers.

And I've been quite pleased and maybe a little bit surprised.

Scott: Pleasantly.

They are seem to be acutely aware of the issues associated with.

Chronic high dose steroid treatment.

And so you know we've got a lot of work to do still in terms of understanding the value that's emerging from the clinical data.

Scott: And certainly we believe that the pricing will be in line with the value that we bring to market.

Todd Tushla: Let's take one final question please.

Operator: Our last question comes from Ami Fadia with Needham. Please go ahead. Ami, your line is open. Please go ahead with your question.

Our last question comes from Amit Bhatia with Needham. Please go ahead.

And Amit Your line is open. Please go ahead with your question.

Todd Tushla: It sounds like I’ll follow-up with Ami later. Kevin?

Okay.

Kevin C. Gorman: Thank you all this morning for your questions. Really appreciate this time to interact, and we’ll be talking a lot more at upcoming meetings. The only closing comments that I have is I hope that you - it’s come through our enthusiasm as we start 2024 here. We do expect to have another great year. The two things that I really want to point out the most as I close here, number one is probably starting three years ago, you saw our investment ramp up in INGREZZA, both with sales force expansions and with DTC efforts. You have now seen in the last two years what a difference that can make. We have a multi-billion dollar product on our hands here, so those investments have got a phenomenal ROI on them. They will continue. Our focus with those investments is on the patient. It’s on building out this very early marketplace that is still - I know I’ve said it for six years, and I’m going to say it into a seventh year, this is just the tip of the iceberg for this. There are so many more patients that need this drug in order to be able to live fulfilling lives.

This time, they interact and we'll be talking a lot more at our upcoming meetings.

The only closing comments that I have is I hope that you it's come through our enthusiasm as we start 2024 here, we do expect to have another great year.

The two things that I really want to point out the most as I close here number one is.

Probably starting three years ago, you saw our investment ramp up in <unk>.

And in grocer, both with sales force expansion.

And with the DTC efforts you have now seen in the last two years, what the difference that can make we have a multibillion dollar product on our hands here. So those those investments have got a phenomenal ROI on them. They will continue our focus with us.

Investments is on the patient it's on building out this very early marketplace that is still I know I've said it for six years I'm going to say it into our seventh year. This is just the tip of the iceberg for this there are so many more patients that need this drug in order to be able to live.

[noise] fulfilling lives with <unk>, it's very much the same way as Matt said the amount of investment that that we need within that marketplace is much smaller because the patient population is much smaller, but nevertheless, I'm very confident that what you will see is the investments that we're making this year.

[noise] fulfilling lives

Kevin C. Gorman: With CRINECERFONT, it’s very much the same way. As Matt said, the amount of investment that we need within that marketplace is much smaller because the patient population is much smaller. But nevertheless, I’m very confident that what you will see is the investments that we’re making this year, next year, are going to be incredible for the lives of those patients, and also as a significant leg of growth for Neurocrine going forward. Then finally, the investments that we’re making in our internal R&D efforts are definitely going to pay off. we get to see a lot more, unfortunately, than you get to see, but I can tell you that in the coming years, you’re going to see those efforts in small molecules, which has always been our strong point, but in all of the large molecules, whether you’re talking about peptides, proteins, antibodies and gene therapies - those will start rolling into the clinic, so we’re very excited here and we have a lot of work ahead of us. We look forward to talking to you more in the future. Thank you very much.

Next year are going to be incredible for the lives of those patients and also as a significant leg of growth for American going forward and then finally, the investments that we're making in our internal R&D efforts are definitely going to pay off when we get to see a lot more.

Unfortunately, then you get to say, but I can tell you that in the coming years youre going to see those efforts in small molecules, which has always been our strong quiet, but in all of the large molecules, whether youre talking about peptides proteins antibodies and gene therapies those will start rolling into the clinic. So we're very excited.

Here.

Speaker Change: And we have a lot of work ahead of US we look forward to talking to you more in the future. Thank you very much.

Operator: This does conclude the Neurocrine Biosciences year-end and fourth quarter results call. You may disconnect your line at this time and have a wonderful day.

This does conclude the Neurocrine biosciences yearend and fourth quarter results call. You may disconnect. Your lines at this time and have a life.

Okay. Hum. [music]. Okay. [music]. Hum. Mhm. [music]. Hum. [music]. Hum. [music]. Yeah. Yeah. Yeah. Yes. Yeah. Okay. Okay. Yeah. [music]. Yeah.

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Q4 2023 Neurocrine Biosciences Inc Earnings Call

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