Q4 2021 Neurocrine Biosciences Inc Earnings Call

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Speaker 2: I.

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Speaker 3: Good day, everyone, and welcome to today's NeuroCren Biosciences reports fourth quarter and year-end results. 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. Please note today's call may be recorded, and I will be standing by should you need any assistance. It is now my pleasure to turn the conference over to Todd Tuchla, Vice President of Investor Relations.

Okay.

Good day, everyone and welcome to today's Neurocrine Biosciences reports fourth quarter and year end results.

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

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

Please note todays call, maybe recorded and I will be standing by should you need any assistance.

It is now my pleasure to turn the conference over to Todd <unk>, Vice President of Investor Relations.

Thank you operator.

Speaker 4: Thank you, operator.

Speaker 4: Good morning and thanks for joining us on our fourth quarter and full year 2021 earnings call.

And thanks for joining us on our fourth quarter and full year 2021 earnings call.

Speaker 4: Joining me today are Kevin Gorman, our Chief Executive Officer, Matt Abernathy, our Chief Financial Officer, Irie Roberts, our Chief Medical Officer, Eric Benovich, our Chief Commercial Officer, and Kyle Gano, our Chief Business Development and Strategy Officer.

Joining me today are Kevin Gorman, our Chief Executive Officer, Matt Abernethy, Our Chief Financial Officer, <unk> Roberts, our Chief Medical Officer, Eric benefits, our Chief commercial officer, and Karl <unk>, Our chief business development and strategy Officer.

Speaker 4: I'd like to remind everyone that during today's 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. After our prepared remarks, we will open the call for your questions. With that, I'll hand the call over to Kevin Gorman.

I would like to remind everyone that during today's 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. After our prepared remarks, we will open the call for your questions with that I'll hand, the call over to Kevin Clark.

Yeah.

Thank you Scott good morning today, we wanted to look back to the challenging 2021, and the lessons we've learned that the progress.

Speaker 5: Thank you, Todd. Good morning. Today we want to look back at a challenging 2021 and the lessons we've learned, the progress we've made. We will also be looking forward to 2022, a year that we believe will set us up for tremendous growth for the next several years.

We will also be looking forward to 2022, a year that we believe will set us up for tremendous growth.

Yes.

Speaker 4: 2021 was bracketed in Q1 and Q4 by rising infections, office closures, and significant staffing shortages that constrained our efforts. However, we did make progress identifying many new healthcare professional customers and how to effectively work with them in a very challenging and changing environment. Eric will go into this in more detail in a moment.

'twenty, one what's bracket that in Q1, and Q4 by rising infections office closures and significant staffing shortages that constrained our efforts. However, we did make progress identifying many new healthcare professional customers and how to effectively work with them in a very challenging and changing environment. Eric will go into this in more.

Detail in a moment.

Speaker 4: Turning our attention to the future, the guidance that released this morning is founded on the lower end by a continuing unpredictable epidemic epidemic that ends and flows. The upper end is less constrained by COVID-19 anticipates reopening of clinics with sufficient staff and the impact in the second half of the year of an expanded sales force more focused on specific points of care than previously.

Turning our attention to the future the guidance that we released this morning is founded on the lower end by continuing unpredictable.

It hasn't been flawless the upper end is less constrained anticipates.

We anticipate reopening of flex with sufficient staff and the impact in the second half of the year of expanded sales force more focused on specific points of care. So previously.

We believe these internal and external events will allow us to bring aggressive many more patients who are needlessly suffering with TD and will lead to significant growth both this year and beyond.

Speaker 4: We believe these internal and external events will allow us to bring rest to many more patients who are needlessly suffering with TB and will lead to significant growth both this year and beyond. We have made a good start in addressing this market and we will now re-accelerate growth.

We have made a good start in addressing this market and we will now reaccelerate correct.

Speaker 4: Concurrent with our commercial efforts, we have developed a neuroscience portfolio second to none. We have 12 Phase II, Phase III programs addressing diseases and disorders in neurology, neuropsychiatry, and neuroendocrinology.

Concurrent with our commercial efforts, we have developed the neuroscience portfolio second to none we.

We have 12 phase II phase III programs addressing season disorders in neurology and neuropsychiatry neuroendocrinology.

We acknowledge the historical challenges in developing medicines for these diseases.

Speaker 4: We acknowledge the historical challenges in developing medicines for these diseases.

Speaker 5: And we have designed this pipeline with multiple compounds, each addressing a different mechanism to treat a specific disease, such as the way we are approaching schizophrenia and the way we're approaching major depression.

And we have designed us pipelines.

With multiple compounds each addressing a different mechanism to treat a specific disease such as the way we are approaching schizophrenia and the way we're approaching major depression.

But the flip side of this we're developing other compounds where each one of these can address multiple diseases.

Speaker 5: But the flip side of this, we're developing other compounds where each one of these can address multiple diseases.

Speaker 4: By attacking diseases from these two fronts, we believe we will be successful in addressing otherwise intractable diseases and disorders. Over the next 18 months, this pipeline will have a number of significant readouts, and Ira will go into these in more detail.

I am talking diseases from these two products. We believe we will be successful in addressing otherwise intractable diseases and disorders over the last 18 months. The pipeline will have a number of significant readouts and I will go into these in more detail.

At this time I would like to turn it over to Matt.

Thanks, Kevin and good morning, since we pre announced Q4 and growth of sales in early January I'm going to focus my remarks on our 2022 sales and operating expense guidance.

Speaker 6: Thanks, Kevin. And good morning. Since we pre-announced Q4 ingress of sales in early January , I'm going to focus my remarks on our 2022 sales and operating expense guidance.

Speaker 6: 2022 Ingresa net sales guidance range is $1.25 to $1.35 billion reflecting our latest thinking considering current trends, environmental factors, and our ongoing business initiatives. This is our first time providing annual sales guidance and we aim to be as transparent as possible about our assumptions.

2022, <unk> net sales guidance range is one $5 billion to $1.35 billion, reflecting our latest thinking considering current trends.

Environmental factors and our ongoing business initiatives.

First time, providing annual sales guidance and we aim to be as transparent as possible about our assumptions.

Our assumptions bonds, a few primary category.

Speaker 6: Our assumptions fall into a few primary categories. The first relates to the.

The first relates to the external environment.

Speaker 6: COVID's impact on our business is clear. As COVID cases go up, psychiatric patient visits decline with a higher mix of visits going virtual.

Covid <unk> impact on our business as clear as Covid cases go up like gastric patient visits decline with a higher mix of visits going virtual.

Those combination directly impact PV diagnose.

Speaker 6: This combination directly impacts TB diagnosis and ultimately treatment rate.

And ultimately treatment rate.

Speaker 6: The good news is that COVID cases are starting to decline and we expect site patient visits to increase throughout 2022, leading to a tailwind for Ingress in the second half of the year. But admittedly, it is difficult to predict how the impact of COVID will transpire.

The good news is that Covid cases are starting to decline and we expect psych patient visits to increase throughout 2022, leading to a tailwind for <unk> growth in the second half of the year, but admittedly it is difficult to predict how the impact of Covid will transpire.

Speaker 6: The second bucket relates to the benefits we expect from our commercial initiative, specifically our direct-to-consumer advertising campaign and Salesforce expansion, which is on track to be fully in place next month.

The second bucket relates to the benefits, we expect from our commercial initiatives.

Specifically, our direct to consumer advertising campaign and sales force expansion, which is on track to be fully in place next month.

Speaker 6: We anticipate these initiatives will help accelerate diagnosis and treatment rates.

We anticipate these initiatives will help accelerate diagnosis and treatment rate.

Speaker 6: On the payer front, access and net revenue per script are expected to remain consistent with 2021. We assume sales seasonality to be very similar to previous years with Q1 having the most disruption due to the typical growth to net dynamics and the impact on refill rates due to the reauthorization process.

On the payer front access and net revenue per script are expected to remain consistent with 2021.

We assume sales seasonality to be very similar to previous years with Q1, having the most disruption due to the typical gross to net dynamics and the impact on refill rates due to the reauthorization process.

Now to our operating expense investments, our 2020 to GAAP operating expense guidance range is $1 1 billion, one 5 billion with investments focused on accelerating in growth or growth.

Speaker 6: Now to our operating expense investment. Our 2022 GAAP operating expense guidance range is $1.1 billion to $1.15 billion, with investments focused on accelerating Ingressive Growth and advancing our many R&D programs.

And advancing our many RMB program.

Speaker 6: Our SG&A investments primarily reflect a $100 million increased spend in the sales force expansion and DCC.

Our SG&A investments, primarily reflect a $100 million increased spend and sales force expansion and DTC.

Speaker 6: In addition, our R&D operating expense reflects advancing 12 mid to late-stage programs in the clinic and also a recently completed in-licensing of an M4 agonist from Sose Heptare.

In addition, our R&D operating expense reflects advancing 12 mid to late stage programs in the clinic and also our recently completed in licensing of <unk> agonist from Societe have par.

Speaker 6: Our strong balance sheet, durable cash flow, and P&L profile allow us flexibility to execute our capital allocation priorities, investing in Growing Ingressa, and advancing our important clinical programs to discover new, innovative therapies for people who deserve better. Now, over to Eric Benevitz.

Our strong balance sheet durable cash flow, Ian P&L profile allows us flexibility to execute our capital allocation priorities.

Investing and growing in <unk>.

And advancing our important clinical programs to discover new innovative therapies for people, who deserve better now.

Now over to Eric benefits.

Speaker 6: Thank you, Matt. Before I begin, I want to acknowledge our commercial and medical affairs.

Thank you, Matt before I begin I want to acknowledge our commercial and medical affairs teams.

Speaker 6: Throughout last year's challenging external environment, your unwavering dedication and commitment made a meaningful difference to many thousands of patients who otherwise would have continued to needlessly suffer from PD.

Brent last year's challenging external environment, your unwavering dedication and commitment made a meaningful difference to many thousands of patients who otherwise would have continued to needlessly suffered from TD.

<unk> Q4 performance marks our third straight quarter of sequential growth during the pandemic era.

Speaker 6: Ingress's Q4 performance marked our third straight quarter of sequential growth during the pandemic era. Total prescriptions grew 8% sequentially and grew 32% versus the prior year.

Total prescriptions grew 8% sequentially and grew 32% versus the prior year.

While it was good to see that kind of growth as Kevin said, we strive to improve while managing through several issues both in and out of our control.

Speaker 6: While it was good to see that kind of growth, as Kevin said, we strive to improve while managing through several issues, both in and out of our control.

Speaker 6: First in Q4, changes to our distribution network were implemented, and as anticipated, we saw modest shifts in scripts going from some of our specialty pharmacies to CVS and Walgreens retail outlets.

First in Q4 changes to our distribution network were implemented.

And as anticipated we saw a modest shift in scripts going from some of our specialty pharmacies, Cvs and Walgreens retail outlets.

Recall, we expanded the distribution network in order to provide even greater ease of access to Reza for patients and their health care providers.

Speaker 6: Recall, we expanded the distribution network in order to provide even greater ease of access to the residents for patients and their healthcare providers.

Speaker 6: The transferring of prescriptions back and forth across our pharmacy network likely led to delayed prescription bills for some of those patients.

The transferring of prescriptions back and forth across our pharmacy network likely led to delays prescription builds for some of those patients.

Speaker 6: Second, while difficult to ascribe how much of an impact first the Delta variant and then the Omicron variant had on TRX and NRX volume, we know the rising cases significantly impacted our customers and interfered with patient care.

Second while difficult to describe how much of an impact first the Delta Berry and then the omicron Varian have on Trs and interact volume, we know the ryzen cases significantly impacted our customers and interfered with patient care SaaS.

Speaker 6: Staff shortages and turnover at offices, clinics, and pharmacies likely contributed to an uptick in cycle time from prescription referral to prescription fill.

Staff shortages and turnover at offices clinics and pharmacies likely contributed to an uptick in cycle time from prescription referral to prescription fill our.

Our persistence and compliance remains strong.

Speaker 6: Our persistence and compliance remain strong, consistent with prior quarters, helping us to maintain momentum going into the new year.

System with prior quarters, helping us to maintain momentum going into the new year.

Speaker 6: All in all, despite a worsening external environment brought on by the surging Omicron variant.

All in all despite a worsening worsening external environment brought on by the surging omicron variants.

Speaker 6: particularly in the second half of Q4. We estimate TD diagnosis rates have now grown to around 25% of the TD population.

Particularly in the second half of Q4, we estimate TD diagnosis rates have now grown to around 25% of the TD population.

With over 56000 total prescriptions in Q4, a record level and graduate continues to be the number one most prescribed treatment for tardive dyskinesia.

Speaker 6: With over 56,000 total prescriptions in Q4, a record level, Ingresa continues to be the number one most prescribed treatment for tardive dyskinesia.

Shifting to this year, we provided the 2022 guidance range break Reza and are now over one month into the year.

Speaker 6: Shifting to this year, we've provided the 2022 guidance range for Ingresa and are now over a month into the year. So what have we seen?

So what do we see.

Speaker 6: The external environment is slowly improving, but no one is out of the woods yet. We've been encouraged with early signals and are cautiously optimistic that access to our key customers will trend positively as the external environment continues to improve.

The external environment is slowly improving but no one is out of the woods yet we've been encouraged with early signals and are cautiously optimistic that access to our key customers will trend positively as the external environment continues to improve.

Speaker 6: Internally, the onboarding effort of our Salesforce expansion is well underway. The newly expanded 350 plus strong Salesforce with dedicated teams across psychiatry, neurology, and long-term care will be fully deployed at the end of this quarter.

Internally the Onboarding effort of our sales force expansion is well underway. The newly expanded 350, plus strong sales force with dedicated teams across the chytrid neurology in long term care will be fully deployed at the end of this quarter.

In addition, we plan to run our ongoing TD spotlight branded direct to consumer campaign throughout 2022.

Speaker 6: In addition, we plan to run our ongoing TD Spotlight branded direct-to-consumer campaign throughout 2022.

Speaker 6: With improving market fundamentals and strong conviction in the commercial investments we are making for Ingresa, the stage is set for accelerated growth in 2022 and for years to come.

With improving market fundamentals and a strong conviction in the commercial investments, we are making very aggressive.

Pages set for accelerated growth in 2022 and for years to come.

<unk>, while we continue to receive positive feedback from patients and neurologists you should not expect a great acceleration in 2022 sales as on Genesis remains a non formulary medication on most Medicare part D plans.

Speaker 6: For Ongentis, while we continue to receive positive feedback from patients and neurologists, you should not expect a great acceleration in 2022 sales, as Ongentis remains a non-formulary medication on most Medicare Part D plans.

And I should reiterate <unk> opens doors to neurology practices and gives our team more time with prescribers highlight both on Genesis and <unk>.

Speaker 6: And I should reiterate, Ongentis opens doors to neurology practices and gives our team more time with prescribers to highlight both Ongentis and Ingressis.

Speaker 6: Furthermore, we strongly believe that having a dedicated neurology team will benefit both products, especially with movement disorder specialists.

Furthermore, we strongly believe that having a dedicated neurology Keith will benefit both products, especially with movement disorder specialists.

Speaker 6: So, with that, I'll turn the call over now to my colleague, Dr. Irie Roberts, for an update on her pipeline. Thank you, Eric, and good.

So with that I'll turn the call over now to my colleague Dr. Ivy Roberts for an update on our pipeline.

Thank you, Eric and good morning to everyone on the call.

Over the last 12 months, we have made tremendous progress across all of research and development.

Speaker 7: Over the last 12 months, we have made tremendous progress across all of research and development.

Speaker 7: We have advanced a novel and diverse pipeline of 12 mid- to late-stage clinical programs, each of which has the potential to be a first-in-class or best-in-class medicine.

We have advanced our novel and diverse pipeline of 12 mid to late stage clinical programs.

Each of which has the potential to be a first in class or best in class medicine.

2021 was in many ways a foundational year for Neurocrine R&D.

Speaker 7: 2021 was in many ways a foundational year for Neurocrine R&D, with the stage now set for a year of unprecedented investment and execution to advance this pipeline.

At this stage now set for a year unprecedented investment and execution to advance this pipeline.

With the goal of submitting a supplemental new drug application for <unk> in Huntington's disease.

Speaker 7: with the goal of submitting the supplemental new drug application for Valbenazine Huntington's disease.

Speaker 7: Initiating a phase 2 study in schizophrenia for NBI 568, the selective M4 orthosteric agonist recently acquired through our partnership with Soce Heptares, and delivering a significant number of registrational and phase 2 data readouts over the next 24 months.

Initiating a phase III study in schizophrenia for MDI five eight the selective and for systemic agonist recently acquired through our partnership with <unk>.

And delivering a significant number of registrational and phase III data readouts over the next 24 months.

I'll spend the balance of my prepared remarks brief status updates across these pipeline programs beginning with broadband.

Speaker 7: I'll spend the balance of my prepared remarks on brief status updates across these pipeline programs, beginning with Val Benazir.

Speaker 7: In the second half of 2022, we plan to submit the SNDA to the FDA for the treatment of Korea associated with Huntington's disease.

In the second half of 2022, we plan to submit the NDA to the FDA for the treatment of chorea associated with Huntington's disease.

Speaker 7: We were extremely pleased with the safety and efficacy results achieved in the CONNECT-HD study. These data, together with six-month follow-up data from the CONNECT-HD2 study, form the basis of our SNVA submission.

We were extremely pleased with the safety and efficacy results achieved in the connect HD study.

These data together with six month follow up data from the connect HD two study form the basis of our NDA submission.

Speaker 7: Continuing with Valbenazine, we recently initiated registration studies for the adjunctive treatment of schizophrenia and for dyskinetic cerebral palsy. We anticipate top learning data from these recently initiated studies in 2023.

Continuing on with broadband as we recently initiated.

Initiated registration studies for the adjunctive treatment of schizophrenia and for disconnecting cerebral palsy.

Anticipate top line data from these recently initiated studies in 2023.

Moving to <unk> for the selected T type calcium channel antagonists and license from Idose yet.

Speaker 7: Moving to NBI-104, the selective T-type calcium channel antagonist in license from Eidosia.

Speaker 7: We expect top-line data from two Phase 2 studies for NBI-104 this year.

We expect topline data from two phase III study.

I went out for this year.

Speaker 7: Somewhere around mid-year, we anticipate delivering proof-of-concept data in essential tremors.

Somewhere around mid year, we anticipate delivering proof of concept data in essential tremor.

Speaker 7: Following that, in the second half of the year, we anticipate completing our ongoing trial in epilepsy with continuous spike and wave during sleep.

Following that in the second half of the year, we anticipate completing our ongoing trial in epilepsy with continuous spike in waves during sleep.

Based on their view of these data generated for MDI, Paul we will determine potential next steps for each of these indications.

Speaker 7: Based on the review of these data generated for MBI-104, we will determine potential next steps for each of these indications.

Turning now to MBIA three five to the selective <unk> six sodium channel inhibitor in license from Dr.

Speaker 7: Turning now to NBI 352, the selective NAV 1.6 sodium channel inhibitor in license from Xenon.

Speaker 7: We have two phase two studies ongoing. The first in SCN8AD, a rare pediatric epileptic encephalopathy, and the second in focal onset seizure in adults, from which we anticipate delivering top line data in 2023.

We have two phase III studies ongoing.

In SDN.

A rare pediatric epilepsy can set philosophy, and the second and focal onset seizures in adults.

We anticipate delivering topline data in 2023.

Speaker 7: Drifting gears now to the psychiatry portfolio of assets in license from Takeda Pharmaceuticals.

Shifting gears now to the psychiatry portfolio of assets and license from Takeda Pharmaceuticals.

Speaker 7: We have initiated phase two studies with all three lead programs, including Lubedaksostat in cognitive impairment associated with schizophrenia, NBI 845 for inadequate response in major depressive disorder and NBI 846 in anhedonia in major depressive disorder.

We have initiated two phase II studies with all three lead programs, including the tax effect and cognitive impairment associated with schizophrenia.

<unk> eight five well in adequate response in major depressive disorder.

MBIA, Inc. Full stake an anecdote in major depressive disorder.

Speaker 7: Hotline data for 845 and 846 are anticipated in 2023.

Top line data for April five in April are anticipated in 2023.

Speaker 7: Staying within psychiatry, I'm the lead muscarinic agonist in our collaboration with Sosa Hepatitis, NBI 568. This molecule is a highly selective orthosteric agonist of N4, with the potential to be a best-in-class molecule against this target. We plan to initiate a phase two study of 568 in North America for the treatment of schizophrenia this year.

Staying within psychiatry, and the lead muscarinic agonist in our collaboration associate hectares MDI 568.

This molecule is a highly selective <unk> agonist eventful with the potential to be a best in class molecule against this target.

Turning to initiate a phase II study of <unk>.

In North America for the treatment of schizophrenia this year.

Speaker 7: And finally, with respect to our neuroendocrinology portfolio, we remain on track to read out top line data for the registrational studies of chronesopods in both the adult and pediatric patient populations in 2023.

And finally with respect to our neuro endocrinology portfolio, we remain on track to read out top line data for the Registrational study of <unk> in both the adult and pediatric patient populations in 2023.

Speaker 7: To close, we have built a strong R&D pipeline that has the potential to dramatically change lives for patients.

To close we have built a strong R&D pipeline that has the potential to dramatically change lives of patients.

Speaker 7: Our focus now is on the effective delivery of this pipeline, while also continuing to add innovative candidates via internal drug discovery and strategic business development, where we believe those efforts can serve the needs of our patients.

Our focus now is on the effective delivery of our pipeline, while also continuing to add innovative candidate buyer.

Internal drug discovery and strategic business development, where we believe those assets consist of knees outpatient.

I want to thank everyone at Neurocrine, our external partners clinicians and patients with a culture in our ultimate mission to bring medicines to patients who need better treatment options.

Speaker 7: I want to thank everyone at Neurocrin, our external partners, clinicians and patients who support us in our ultimate mission to bring medicines to patients who need better treatment options.

Speaker 7: I'll now hand the call back to Kevin. Thank you, Kevin. Thank you, Irene. That concludes our prepared remarks and we are ready to open it up for questions.

I'll now hand, the call back to Kevin. Thank you Kevin. Thank you that concludes our prepared remarks, and we're ready to open it up for questions.

Speaker 1: And at this time, if you would like to ask a question, please press the star and 1 on your touch-tone phone. You may withdraw your question at any time by pressing the pound key.

And at this time, if you would like to ask a question. Please press the star and one on your Touchtone phone.

Draw your question at any time by pressing the pound key.

We'll move first to Phil Nadeau with Cowen. Please go ahead.

Speaker 1: We'll move first to fill in the dough with Cowan. Please go ahead.

Good morning, Thanks for taking my question a question on essential tremor can you give us some sense of what would be proof of concept for you.

Speaker 4: Good morning. Thanks for taking our question. A question on essential tremor. Can you give us some sense of what would be proof of concept for you and what would warrant further development? Thank you.

And what would warrant further development. Thank you.

Speaker 7: Thanks very much, Bill, and yes, certainly. As you know, we have a proof-of-concept study ongoing, which is a 28-patient crossover study. We have several endpoints in that study. The primary endpoint actually looks at tremor amplitude and is measured by accelerometer, but we also have the TETRIS measures in that patient population of moderate to severely impacted tremor patients. I think we'll be looking at the data in totality. Obviously, we'll be interested in seeing a statistically significant difference in the crossover design, but beyond that, we'll be looking at the data in totality, including also a CGI assessment as well. And then with those data in hand, sometime around the middle of this year, we'll be considering our next steps if we're successful in that regard.

Thanks, very much bill.

Yes, certainly as you know we have a proof of concept study ongoing which is the 28th patient crossover study and we have several endpoints in that study.

Primary endpoint actually looks at tremor amplitude and is measured by accelerometer, yet, but we also have the Texas measures in that patient population of moderate to severely impacted China.

The patient.

I think we will be looking at the data into policy I don't think they will be interested in seeing a statistically significant difference in the <unk>.

The design, but beyond that we'll be looking at the data into policy, including also at CGI.

Testament, as well and then with real estate to enhance sometime around the middle of this year, we'll be considering on next steps if we're successful in that regard.

Speaker 8: Perfect, thank you.

Perfect. Thank you.

Yes.

And next to masses.

Speaker 1: And we'll move next to Paul Mathis with Dr. Seeple. Please go ahead.

Stifel. Please go ahead.

Speaker 4: Great, thanks so much for taking the question. On your Ingressa guidance, I was wondering if you could kind of frame for us at the low, midpoint, and high end, how demand growth in those different scenarios compares to what you were seeing before the COVID pandemic. Thanks so much.

Great. Thanks, so much for taking the question on your Ingressive guidance I was wondering if you could kind of frame for us at the low midpoint and high end how demand growth from those different scenarios compares to what you were seeing before.

The COVID-19 pandemic. Thanks, so much.

Yes, Thanks Paul.

Speaker 9: Yeah, thanks, Paul. As you as you look back before the pandemic, you know, we had a nice growth trajectory of, you know, call it a couple hundred million dollars a year. So when you think about a 20% midpoint growth, you know, it pretty much puts you back on track with how we were going.

Look back before the pandemic, we had a nice growth trajectory of call. It a couple of hundred million dollars a year. So when you think about 20% midpoint growth.

It pretty much puts you back on track with how we were going.

Speaker 9: prior to the pandemic. I think the two biggest items that I'd point to as it relates to the guidance range is, one, the environment. As the environment cooperates, patients going back into the office,

Prior to the pandemic I think the two biggest items that I'd point to as it relates to the.

The guidance range is one of the environment.

The environment cooperates patients going back into the office.

Speaker 9: and access to customers is greater, you would expect us to fall higher on the range.

And access to customers is greater you would expect us to fall higher on the range.

Speaker 9: If the pandemic continues to have significant pressure, you know, that would that would, of course, put you closer to the to the bottom of the range and impacting overall demand. The second piece has been on the business initiative side. We're well underway on our sales force expansion that we expect to complete by the end of this quarter, which will benefit us in the second half of the year.

Pandemic continues to have significant pressure.

That would of course put you closer to the to the bottom of the range and impacting overall.

Demand the second piece has been on the business initiative side, we're well underway on our sales force expansion that we expect to complete by the end of this quarter, which will benefit us in the second half of the year and were optimistic with what we've been seeing recently and with the case counts going down and what we're seeing internally. So we're look.

Speaker 9: And we're optimistic with what we've been seeing recently and with the case counts going down and what we're seeing internally. So we're looking forward to a nice year, another nice growth year for Ingresa.

In forward II.

A nice year.

Nice growth year for Grubhub.

Thank you.

And we'll move next to <unk> from Bank of America.

Speaker 1: We'll move next to Tazina Maud from Bank of America. Please go ahead.

Please go ahead.

Speaker 10: Hi, good morning and thank you for taking my questions. Just the point of clarification. Is your guidance with, or without impact from inventory stocking for. And then.

Hi, Good morning, and thank you for taking my question.

Just a point of clarification is your guidance with or without impact from inventory stocking or <unk>.

And then.

Speaker 10: how much of your upper end of guidance is based on the potential for psychiatrists to, you know, continue to be reimbursed for their televisits at the same level as in person, let's say, for the rest of the year? And if there is a place for upside, would it be that particular variable or is there something else? Thanks.

How much of your upper end of guidance is based on the potential for psychiatrist too.

Continue to be reimbursed for their tower business at the same level as in person, let's say for the rest of the year and if there is a place for upside would it be that particular variable or is there something else. Thanks.

Hey, good morning, Susan.

Speaker 5: Hey, good morning, Suzeen. I'll take the second part of your question first, and that is that within our full range of guidance, we anticipate that there will be no changes to telehealth throughout the entire year.

I'll take the second part of your question first and that is that within our full range of guidance.

We.

I anticipate that there will be no changes.

Health throughout the entire year.

Matt and you would've thought that yes, that's on the reimbursement front, we of course would expect.

Speaker 9: Matt, do you want to talk about? Yeah, and that's on the reimbursement front. We, of course, would expect, you know, as as the clinics open up from the COVID shutdown, that there would be a higher mix of a patient. This is a person. But from a reimbursement perspective, our current census.

As.

Clinics open up.

The COVID-19 shutdown, but there would be a higher mix of patient visits in person, but from a reimbursement perspective. Both current senses is policies like we are not going to be change. This this year on the.

Speaker 9: His policies likely are not going to be changed this year.

Speaker 9: On the inventory front, you know, my strong desire is to get rid of talking about inventory fluctuations quarter to quarter. And, you know, usually within a year it nets out.

Inventory front, my strong desire to get rid of talking about inventory fluctuations quarter to quarter and usually within a year. It nets out so I.

Speaker 9: So, you know, I would say that our guide really reflects the underlying demand for ingressive sales and

I would say that our guide really reflects underlying demand for and growth of sales.

Speaker 9: I will, of course, be continuing to update our guide at the end of each quarter, which would, you know, take into account any learnings or thinking around inventory. And the only other thing I would add to that is that, you know, reiterate what Matt said, over a year's period of time, any inventory fluctuations net out. And as we've seen now over multiple quarters, the amount of inventory that's carried out in Grants is actually very small compared to the Fed's.

We will of course be continuing to update our guide at the end of each quarter, which would take into account any learnings or thinking around around inventory and then the only other thing I would add to that is that reiterate.

To reiterate what Matt said over a year's period of time any inventory fluctuations net out and as we've seen now over multiple quarters.

Mount of inventory that is carried out in glass is actually very small compared to the first.

Okay. Thank you.

And we'll take our next question from Brian Abrams with RBC capital markets. Please go ahead.

Speaker 1: And we'll take our next question from Brian Abrams with RBC Capital Markets. Please go ahead.

Speaker 4: Hey, good morning guys, thanks for taking my question and congrats on all the progress and otherwise challenging year.

Hey, good morning, guys. Thanks for taking my question and congrats on all the progress in an otherwise challenging year.

Speaker 4: A question on commercial investment. It sounds like investments are going to start to pull through.

A question on commercial investment it sounds like investments are going to start to pull through.

From the expanded sales force as the year progresses, I guess I'm curious in medium term as we exit the year, what's the right way to think about the returns that youre going to get there how did the incremental dollars put towards these additional segments youre going to pursue like long term care translate to revenue compared to the current areas Youre in and I'm also curious how much interest.

Speaker 4: from the expanded sales force as the year progresses. I guess I'm curious in medium term as we exit the year, what's the right way to think about the returns that you're hoping to get there? How do the incremental dollars put towards these additional segments you're going to pursue like long-term care translate to revenue compared to the current areas you're in? And I'm also curious how much intrinsic growth is left in your current target areas as well beyond just the reopening benefits. Thanks.

<unk> growth is left in your current.

Market areas as well beyond just the preopening benefits. Thanks.

Speaker 6: Good morning. So, you know, I think the way to think about it is that, you know, with these, with the expansion and the reorganization of our field sales team, essentially, we're going deeper into existing segments, you know, for example, the build out of a dedicated neurology team allows us to reach more neurologists and to see them more frequently than we've been able to do thus far in the commercial ramp.

Good morning.

The way to think about it is that.

With these with the expansion and the reorganization of our field sales team essentially we're going deeper into existing segments for example.

The build out of a dedicated neurology team allows us to reach more neurologists and to see them more frequently than we've been able to do thus far in the commercial ramp.

Speaker 6: With the build-out of an LTC team, essentially it's going into a care segment that we were always interested in from the get-go but didn't really have the wherewithal to really put a dedicated focus against.

With the build out of an LTC team essentially it's going into a carrier segment.

We are always interested in from the get go but didn't really have the wherewithal.

To really put a dedicated focus against and one way to think about LTC is essentially adjacent to.

Speaker 6: And, you know, one way to think about LPC is essentially adjacent to the psychiatry space, you know, there are providers that practice in both.

The psychiatry space there are providers that practice in both.

Speaker 6: psychiatry clinics, as well as going into residential care facilities.

Psychiatry clinics as well as going into a residential care facilities.

Speaker 6: And, you know, essentially, this is a logical next step for us. So, you know, this is obviously an expansion of our field sales team, you know, that's allowing us to tackle and reach more providers.

And.

Essentially this is a logical next step for us so.

This is obviously an expansion of our field sales team, that's allowing us to tackle and reach more providers.

Speaker 6: But at the same time, it's allowing us to go deeper within the existing base of providers. And I think it's really a function of where we are in the commercial ramp for Ingresa. About five years now, and there's certainly more prescribers.

But at the same time, it's allowing us to go deeper with within the existing base of providers and I think it's really a function of where we are in the commercial ramp frame breza about five years now.

There is certainly more prescribers.

Speaker 6: than what we had in the early phase of the launch. And there's certainly more high value potential prescribers that we've identified. The other thing I would note is this allows us to put a little bit more focus on, you know, what's been an emerging high priority segment.

Then what we had in the early phase of the launch and Theres certainly more high value potential prescribers that we've identified the.

The other thing I would note is this allows us to put a little bit more focused on what's been an emerging high priority segments of prescribers, which is advanced practice providers, meaning nurse practitioners and physician assistance.

Speaker 6: of prescribers, which is advanced practice providers, meaning nurse practitioners and physician assistants that go across all of those sites of care. So, you know, the way to think about it is, you know, we're going deeper into the existing segments, and, you know, we're tapping into a new opportunity in long-term care, and also provide, providing, you know, more insight as we move through the year and get into 2023.

That go across all of those sites of care.

The way to think about it is we're going deeper into the existing segments and we're tapping into a new opportunity in long term care and also provide be providing.

More insight as we move through the year and get into 2023.

Thanks, so much.

Speaker 1: We'll move next to a new POMRAMA with J.P. Morgan. Please go ahead.

We'll move next to our new <unk> Rama with Jpmorgan. Please go ahead.

Speaker 9: Hey, guys. Thanks so much for taking the question. I was wondering if we could dig in a little bit into 1Q dynamics specifically. I think at the conference, you talked about 5,300 per script, which is in line with 4Q. But is there any other color you'd want to provide on 1Q specifically? I think previously, you've given a little bit more color and guidance on 1Q, just worried about numbers going all over the place.

Hey, guys. Thanks, so much for taking the question.

I was wondering if we could dig in a little bit into <unk> dynamics, specifically I think at the conference you talked about 5300 per script, which is in line with <unk>, but is there any other color you would want to provide an.

<unk>, specifically I think previously you've given.

Given a little bit more color and guidance on <unk>, just kind of worried about numbers going all over the place.

Okay.

Speaker 9: Yeah, thanks Anupam. And as you said, Q1 always has some dynamics. The growth in that discount, you have patients going through a reauthorization process that ultimately delays their first bill and results in a lower refill rate per patient during the first quarter. So yeah, it is always a bit noisy from a seasonality perspective. Typically, you see Q4 and Q1, a bit of a pullback in Q1 because of the net revenue per strip going down.

Yes, thanks on a bomb and as you said Q1 always has some dynamics the gross to net discount you'll have patients going through a reauthorization process. Ultimately delivered first bill and result in a lower refill rate per patient.

During the during the first quarter. So yes, it is always a bit noisy.

From a seasonality perspective, typically you see Q4 to Q1 a bit of a pullback in Q1 because of the net revenue per script going down.

Speaker 9: and then also the slight impact on the refill rate per patient. And then you see a nice recovery in Q2 and throughout the year.

And then also the slight impact on the refill rate per patient and then you see a nice recovery in Q2 and throughout the year since we're providing an annual guide we're going to get out of some of the specificity that we've historically provided within a quarter, but of course as we exit <unk>.

Speaker 9: Since we're providing an annual guide, you know, we're going to get out of some of the specificity that we've historically provided.

Speaker 9: within a quarter, but of course, as we exit Q1, we'll be taking into account our performance in Q1, what we're seeing, and we'll modify our guide accordingly.

Q1 will be taking into account our performance in Q1, what we're seeing and we'll modify our guide.

Accordingly, but.

Speaker 9: You know, as we historically said, Q1 is Q1, and the goal in Q1 is to ensure that patients stay on medication.

As we've historically said Q1 is Q1 and the goal in Q1 is to ensure that patients stay on medication and that ultimately sets us up for a strong rest of the year.

Speaker 9: And that ultimately sets us up for a strong rest of the year.

Speaker 6: Yeah, I'll chime in here and just add that, you know, obviously, with the surge and the Omicron variant in late Q4 and early Q1,

Yes.

I'll chime in here and just add that obviously.

With the surge in the Omicron variant in late Q4 and early Q1.

Speaker 6: You know that presented, you know additional challenges for us to deal with, you know, certainly that affected our customers

Presented.

Additional challenges for us to deal with certainly that affected our customers.

Speaker 6: with a lot of clinics having staff shortages, providers, you know, falling ill and so on. It affected a good chunk of our sales team as well with a number of our team members needing to quarantine. The good news is that things appear to be getting better. You know, we're cautiously optimistic, you know, that we're seeing an improving external environment. And certainly that benefits our business. And the only thing I would add to that, I'm a father.

With a lot of clinics, having staff shortages providers.

Falling ill and so on.

<unk>.

A good chunk of our sales teams as well with a number of our team members needing to to quarantine.

The good news is that things appear to be getting better we're cautiously optimistic.

Of that we're seeing an improving external environment.

And certainly that benefits our business and the only thing I would add to that on upon this debt.

Speaker 5: The commercial team put a lot of pre-positioned effort in place, starting actually in Q4, in order to help with what we said was looking like it was going to be a very challenging Q1. I think those efforts are going to come to fruition. Like Eric said, I think the best way to put it is we're cautiously optimistic, and improving environment can only help.

The commercial team put a lot of pre positioned effort in place starting actually in Q4 in order to help with.

What we said was looking likely was going to be a very challenging Q1, I think those efforts are going to come to fruition, let Eric said I think the best way to put it is we're cautiously optimistic and improving environment can only help.

Yeah.

Thanks, so much for taking our question.

And we'll move next to Carter Gould with Barclays. Please go ahead.

Speaker 1: We'll move next to Carter Gould with Barclays. Please go ahead

Speaker 11: Great. Good morning. Taking the questions. Maybe one for Irie. Just as we think about coming back to 104, think about read through from the essential tremor study to the epilepsy data later in the year. Are there, I guess, are there specific data that would come out of the ET study that might have some positive read through or de-risk?

Great. Good morning, taking the questions maybe one for Irene.

As we think about coming back to 104 think about read through from the essential tremor study to the epilepsy data later in the year.

I guess the specific data that will come out of the <unk> study that we might have some positive read through or de risk. The <unk> study and then you guys have always talked about more broadly.

Speaker 11: the ET study, and then you guys have always talked about more broadly the potential for additional indications. Are there specific signals from that ET study that might be, you know, insightful as you think about, you know, future indications?

The potential for additional indications other specifics signals from that study that that might be.

Insightful as you think about.

Future indications thank you.

Speaker 7: Yeah, thanks very much. So we know that the calcium channels, the ketocalcium channels that are impacted by 104

Yeah, Thanks, very much and so we know that the.

Calcium channels the T type calcium channels that are impacted by one off Paul.

Speaker 7: are represented within that tremor network and that that tremor network also links very directly to epilepsy from a mechanistic perspective. So actually, in terms of information that we're able to generate from the ET study, I think it is helpful in understanding the pharmacodynamic effect of medication and some of the dose related issues in using 104. In addition, obviously, we will get initial tolerability information in a patient population from the ET study that is in some way relevant to our CSWS study, but obviously it's a very different population. And if you think about CSWS, it's a rare pediatric epileptic encephalopathy, and the patient in that study will be aged two upwards. And so it is different from the ET population, which is a significantly older adult population. So I think in general, we'll be looking at the totality of both the efficacy data from the ET program and the initial safety and tolerability. And we won't have to wait very long to understand the actual signal in the CSWS space anyway, since we will be reading out the data from that 24 patient phase two study in CSWS in the latter part of the year as well.

<unk> represented within not trim, a network that <unk> network also links directly to epilepsy from a mechanistic perspective, so actually Tim.

<unk> of.

Information that we're able to generate from the <unk> study I think it is helpful in understanding the.

Pharmacodynamic effect of medication and some of the dose related issues and using winter fall.

In addition, obviously we look at initial Tolerability information in a patient population from the <unk> study that is in some way relevant to DSW at steady, but obviously, it's a very different population.

If you think about <unk>.

Rare pediatric epilepsy can set philosophy and the patients in that study will be aged two upwards. So is different from the ETE population, which is significantly older adult population.

In general we'd be looking at.

The totality of the.

The efficacy data from the <unk> program and the initial safety and Tolerability and we won't have to wait very long to understand the actual signal dsw's faced any way since we will be reading out the data from that 24 patients.

The phase II study in CSW, Aston and Aqua part of the year as well.

And clearly we can do it.

Speaker 1: We'll move next to Nina Petrito-Garg with Citi. Please go ahead.

Let's move next to Neena <unk> Garg with Citi. Please go ahead.

Speaker 12: Thanks for taking my question. I'm just going back to aggressive guidance. I'm just wondering if you can give us a sense of how you're thinking about the proportion of in person patient visits versus telehealth at the low midpoint and high end of the range and whether the CMS decision that you've talked about previously.

Hey, guys. Thanks for taking my question.

So just going back to guidance.

Just wondering if you can give us a sense of how you're thinking about the proportion of in person patient visits versus telehealth at the low midpoint and high end of the range and weather.

CMS decision that you've talked about previously.

Speaker 12: on having patients seeing psychiatrists having their first

Having patients seeing psychiatrist having their first.

Speaker 12: is it in person and then every year after that whether that'll be a 2022 or more likely 2023.

Is it in person and then every year after that.

Whether that will be a 2022 or more likely 2023 of them.

Yes.

Speaker 6: Yeah, um, the way that we're thinking about telehealth is that, you know, certainly in a

The way that we're thinking about telehealth is that certainly.

Impacts different portions of our business differently.

Speaker 6: impacts different portions of our business differently.

Speaker 6: Ultimately, it's utilized quite a bit, has been utilized quite a bit, and continues to be utilized at a high rate within psychiatry.

Ultimately, it's utilized quite a bit has been utilized quite a bit and continues to be utilized at a high rate within psychiatry.

Speaker 6: you know, the latest data that we've seen is that it's still about half of all patient visits are virtual in psychiatry, whereas in neurology, it's less than 10%. Frankly, it's

The latest data that we've seen is that it's still about half of all patient visits are virtual in psychiatry, whereas in neurology, it's less than 10% frankly, it's.

Speaker 6: it's returned to pretty close to what it was pre-COVID and telehealth is utilized to a much, much lesser degree in LTC, for example. And so, you know, our expectation is that, you know, even after the public health emergency is lifted, that there's going to be a significant utilization of telehealth in psychiatry.

It's returned to pretty close to what it was pre COVID-19 .

And telehealth is utilized to a much much lesser degree in LTC for example, and so.

Our expectation is that.

Even after the <unk>.

Public health emergency is lifted that theres going to be a significant utilization of telehealth in psychiatry, and we've baked that into our planning and our assumptions.

Speaker 6: And, you know, we've baked that into our planning and our assumption.

Speaker 6: The second part of your question was really around some of the guardrails that are being proposed, such as having a first visit requirement be in-person, and at least once a year, in-person visits for subsequent telehealth visits to be reimbursed. We're certainly supportive of making sure that...

The second part of your question was really around some of the guard rails that are being proposed such as having a first visit requirement be in person.

And at least once a year in person visits for subsequent telehealth visits to be reimbursed.

We are certainly supportive of making sure that.

Speaker 6: that patients have the opportunity to see their providers in person. We recognize the value that telehealth provides in certain circumstances but want to make sure that there are guardrails in place going forward. So we'll see how things shake out but you know for the for the duration of 2022 our expectation is status quo.

That patients have the opportunity to see their providers in person, we recognize the value that telehealth providers in certain circumstances, but want to make sure that our guardrails in place going forward. So we'll see how things shake out but for the for the duration of 2022, our expectation is status quo.

Got it thank you.

Speaker 1: And we'll move next to Brian Scorney with Baird. Please go ahead.

We'll move next to Brian Kearney with Baird. Please go ahead.

Hi, This is Luke <unk> on for Brian Thanks for taking our question.

Speaker 6: Hi, this is Lou Kerman. I'm for Brian . Thanks for taking our question. Could you just discuss a bit your expectations for how an approval in Korea and Huntington disease could impact in Greta's growth rate? And do you expect the sequencing of uptake and that indication to be more front loaded or occur to gradual pace? Thanks.

Could you just discuss a bit your expectations for how an approval in Korea in Huntington disease could impacting <unk> growth rate and do you expect the sequencing of uptake in that indication to be more frontloaded or occur at a gradual pace. Thanks.

Yes.

Speaker 6: Yeah, so, you know, first of all, I want to want to emphasize that we need to, we need to finish the, the open label study and get the SNDA submitted.

First of all.

I want to emphasize that we need to we need to.

Finished.

The open label study and get the.

SMB as submitted.

Speaker 6: But assuming that we're successful and we get a label expansion in 2023, you know, we're very excited about the opportunity to bring Angreza to a new patient population, those patients with Huntington's that are experienced in Korea.

But assuming that we're successful and we get a label expansion in 2023.

Very excited about the opportunities to bringing <unk> to a new patient population those patients with Huntington's that are experienced in Korea.

Speaker 6: The way to think about it is that it's all incremental to our business, you know, we're not getting any, essentially any of those Huntington patients now. The health plans, you know, because this is a specialty product and it's a prior authorization process.

The way to think about it is that it's all incremental to our business, we're not giving any.

Essentially any of those huntington's patients now the health plans.

This is a specialty product and there's a prior authorization process.

Speaker 6: You know, they're proving ingressive for TD, but essentially not for other uses. So, you know, we're looking forward to the opportunity to expand the label. And the second part of your question was really around, you know, would this be front-loaded or, you know, would this be a more gradual ramp?

They are proving aggressive for TD, but essentially not for other uses so.

We're looking forward to the opportunity to expand the label in the second part of your question was really around would this be frontloaded or would this be a more gradual ramp.

Speaker 6: You know, we can provide a little bit more color when we get further down the road and we have a sense of what the labeling is going to look like.

Can provide a little bit more color when we get further down the road and we have a sense of what the labeling is going to look like.

Speaker 6: Ultimately, I will say that, you know, we view the

Ultimately I will say that we view the.

Speaker 6: patient opportunity within Huntington's Korea as a group of patients that have unmet medical needs.

Patient opportunity within Huntington's chorea as a group of patients that have unmet medical need only about 20% of the patients with Huntington's chorea are currently treated with a <unk> inhibitor. So certainly there is an opportunity for a differentiated product like <unk> to come in.

Speaker 6: Only about 20% of the patients with Huntington's pria are currently treated with a VMAF2 inhibitor.

Speaker 6: So certainly there's an opportunity for a differentiated product like Ingreza to come in and, you know, to potentially benefit many thousands more patients with Huntington Chorea. So stay tuned for more as we make progress in pursuing that label.

And to potentially benefit many thousands more patients were coming in Korea, So stay tuned for more as we make progress.

In pursuing that that label expansion and the only thing I would add to that is that.

Speaker 5: And the only thing I would add to that is that, obviously, having a dedicated neurology sales force now in Greza will help with that uptake, and they can, at the time of approval, can start focusing their efforts on treating these TD patients, these IHD patients.

Obviously, having a dedicated neurology sales force now with being aggressive will help with that uptake.

At the time of approval can start focusing their efforts on treating these TD patients.

AHD basis. Thank you.

Okay.

Speaker 1: And we'll move next to Miles Mentor with William Blair. Please go ahead.

We'll move next to Myles Minter with William Blair. Please go ahead.

Speaker 4: Oh, hey, just back on the channel, Lincoln Tree for Ingressa.

Hey, just back on the channel inventory for them.

The new sort of steady state that you'd be expecting moving forward with your growth projections I think of headset a program the 10 million number.

Speaker 4: The new sort of steady state that you'd be expecting moving forward with your growth projections, I think I've heard sort of around the 10 million number be thrown around previously, but that seems to have been creeping over time. So just wondering what the new set point is there for our infantry. Thanks.

Sorry, and around previously, but that seems to be creeping over time. So just wondering about the new set point is that for our inventory.

Hi, Myles could you clarify you are asking about what.

Speaker 9: Miles, could you clarify, you're asking about what typical inventory stocking levels would be for... Yeah, and also your projections moving forward with your anticipated growth rates, is that going to change over time?

Typical inventory stocking levels would be for <unk>.

And those are your projections moving forward with your anticipated growth rates is that going to change over time. Thanks.

Yes, no I think we'd look at it from a days on hand perspective, which would take into account any of our volume growth you would typically in our channel seat two to three weeks of inventory on hand, and as you mentioned.

Speaker 9: Yeah, no, I think from a we'd look at it from a days on hand perspective, which would take into account any of our volume growth, you would typically in our channel see two to three weeks of inventory on hand. And as you mentioned, it had grown from call it two weeks to about three weeks. And we're somewhere in between there right now. So, you know, our goal is, you know, we don't influence channel stocking.

Rone.

Call. It two weeks to about three weeks and we're somewhere in between there right now so our goal is.

We don't influence channel stocking.

Speaker 9: You know, we really are somewhat hands off with our distributors.

We really are somewhat hands off with our distributors.

Speaker 9: a product for a variety of reasons, but I think a two to three week days on hand is what you should expect. And it's become, as Kevin said earlier, a less meaningful number quarter to quarter. You know, of course, if there's some major fluctuation, we'll be transparent as always. But, you know, as you think about annual guide, you know, it should net out for the most part throughout the year from a days on hand perspective.

Product for a variety of reasons, but I think two to three week days on hand is what you should expect and it's become as Kevin said earlier.

A less meaningful number quarter to quarter of course, if there is some major fluctuation will be transparent as always.

But as you think about an annual guide it should net out for the most part throughout the year from a from a days on hand perspective.

So thanks.

And we'll move next to Josh <unk> with Evercore. Please go ahead.

Speaker 1: And we'll move next to Josh Shimmer with Evercore. Please go ahead.

Thanks for taking my questions are you planning additional boost of activities. This year and what is your appetite for larger deals and then Matt you just indicated your your hands off with distributors with respect to inventory for a variety of reasons can you share what some of those recent sir thanks.

Speaker 13: Thanks for taking the questions. Are you planning additional business activities this year and what is your appetite for larger deals? And then Matt, you just indicated your your hands off with distributors with respect to inventory for a variety of reasons. Can you share what some of those reasons are?

Speaker 9: Yeah, one of the reasons is just for purposes of causing undue volatility in our sales projection.

Yes, one of the one of the reasons is just for purposes of causing undue volatility in our sales projections.

Speaker 9: our sales performance. I think there are some practices that really incentivize stocking, whether giving incremental discounts or whatnot, to hit a target number. And we just don't want to be in a place where we're overly influencing.

Our sales performance I think there is some practices really incentivize stocking, whether giving incremental discounts are.

Or whatnot.

That number and we just don't want to be in a place where we are.

Overly influencing.

Speaker 9: you know, our sales results. We try to talk more towards underlying demand.

Our sales results, we try to talk more towards underlying demand.

Speaker 9: which is why we've always provided TRX, and I would just say that's the one of the primary.

It's why we've always provided to your active would.

To say that.

That's the.

One of the primary reason.

Speaker 9: And, you know, discourage speculative buying.

And discourage spec.

Speculative buying.

As far as.

Speaker 5: And as far as business development, I'll turn that over to Kyle Gano, our chief of business development. Hi, Josh. Good morning. On the BD side of things, just to recap kind of our order of priorities here at NERC. And obviously, we are investing heavily in Greza and Valbenazine and probably the BMAT2 franchise. And second to that is the pipeline and business development. So we are still looking and active out there looking to bring things into the pipeline, if it makes sense.

Business development, I'll turn that over to Kal Dana or Keith This is no alright, Josh good morning.

On the BD side of things just to recap kind of by order of priorities here at Neurocrine obviously.

We are investing heavily in Gaza and bell benzene and broadly that would be not to franchise and second to that is the pipeline and business development. So we are still looking and active out there with them to bring things into the pipeline that it makes sense I think from our mid to long term objectives, we continuously assess all types of opportunities.

Speaker 9: I think from our mid to long term objectives.

Speaker 9: We continuously assess all types of opportunities ranging from, you know, traditional licensing deals and collaborations to things that are more strategic. So if we can find things that make sense and work for us, we'll look at bringing those in. And I think that you've seen that done over the past few years in the pipeline currently with the assets that we have in mid to late stage development. We do not constrain.

<unk> ranging from traditional licensing deals and collaborations with things that are more strategic so if we can find things that make sense and work for us we'll look at bringing those in.

I think that you've seen done over the past few years and the pipeline currently.

With the assets. So we havent admittedly at stage development that we do not constrain ourselves.

Thank you.

Speaker 1: And we'll take our next question from David Amslam with Piper Sandler. Please go ahead.

And we'll take our next question.

David.

With Piper Sandler. Please go ahead.

Speaker 13: Thanks. So, regarding the long-term care opportunity, you talked about this being a newer opportunity, and I may have missed this. Can you just talk about what portion of the TD market is long-term care-based, and how you should think about, how we should think about, you know, underlying not just volume potential here, but, you know, even sales potential to the extent that you can quantify that. Thank you.

So regarding the long term care opportunity.

Talked about this being a newer opportunity and I may have missed this could you just talk about what portion of the TV market is long term care base and.

How you should think about how we should think about.

Underlying that is volume potential here, but.

Even sales potential to the extent that you can quantify that thank you.

Yes, we havent given any guidance.

Speaker 6: Yeah, we haven't given any any guidance specifically around, you know, what the sales expectations are for long term care. But, you know, the way to think about it is that the way or the way that we think about long term care is that really represents

Typically around what the sales expectations are for long term care.

But the way to think about it is that the way our the way we think about long term care is it really represents.

Speaker 6: a few different types of residential care facilities that treat residents or patients.

A few different types of residential care facilities that treat.

Our residents are patients.

With.

Speaker 6: with the antipsychotics and dopamine-blocking drugs that cause PD. And so that would include, you know, geriatric nursing homes. That might include facilities that treat patients with intellectual or developmental disorders. That would include...

With the.

And a psychotic and dopamine blocking drugs that cause TD.

And so that would include.

Geriatric nursing homes that might include.

Facilities that treat patients with intellectual and developmental disorders.

That would include.

Speaker 6: residential care facilities or assisted living facilities for those with behavioral health conditions. And so, ultimately, you know, if you look at that roll-up, you know, that represents several million people across the U.S. that are in those facilities.

Residential care facilities are assisted living facilities for those with behavioral health.

Our conditions and so ultimately if you look at that roll up.

That represents.

Several million people across the U S that are in those facilities.

Speaker 6: And at any given time, you could expect somewhere between 15% and 30% of those individuals.

And at any given time.

You could expect somewhere between 15, and 30% of those individuals to be announced psychotics.

Speaker 6: to be on antipsychotics and, you know, obviously a subset of them having PD. So, you know, where it shakes out in terms of the size of the addressable patient population with PD in LTC.

Obviously, a subset of them having TD so.

Where it shakes out in terms of the size of the.

Addressable patient population with PD in LTC versus the overall.

TV prevalent population remains to be seen but we certainly feel like and believe based on the.

Early experience that we have in that space.

It's a significant.

Incremental opportunity in.

Segment that we are interested in going into early in the launch, but like I said earlier that we didn't have the resources and the capacity to focus on it. So I think you'll be getting a lot more color and perspective as we make progress.

Speaker 6: But I will say that we're just getting our team hired and trained. They'll be deployed as we exit Q1, and really for the next couple of quarters, we'll be doing a lot to really better characterize that opportunity and set ourselves up for success as we exit 2022 and get into 2023.

But I will say that we're just getting our team hired and trained there'll be deployed as we exit Q1.

And really for the next couple of quarters that we'll be doing a lot to really better characterized that opportunity and set ourselves up.

<unk> set ourselves up for success as we exit 2022 and get into 2023.

Thank you.

Oh.

Speaker 1: And I think our next question from Jay Olsen with Oppenheimer, please go ahead.

Our next question from Jay Olson with Oppenheimer. Please go ahead.

Speaker 13: Hey, congrats on all the progress and thank you for this update since the total addressable TD market in the US is now 600,000 patients. Can you comment on how fast that population is growing? And with the twenty five percent of patients diagnosed, can you talk about your goal for the ultimate level of TD diagnosis as you continue your education and awareness initiatives? Thank you.

Oh, Hey, congrats on all the progress and thank you for this update.

Since the total addressable TV market in the U S is now 600000 patients could you comment on how fast that population is growing and with the 25% of patients diagnosed.

Can you talk about your goal for the ultimate level of TD diagnosis as you continue your education and awareness initiatives. Thank you.

Yes so.

Speaker 6: Yeah, so, um, you know, our, our estimate is around 600,000 people in the US with with Tardive Dyskinesia. And that's, um, you know, based on

Our estimate is around 600000 people in the U S with tardive dyskinesia and Thats.

Based on.

Speaker 6: a meta-analysis of the literature, as well as looking at claims data, etc., and we periodically reassess this. This is a growing population, and it's really a function of the

A meta analysis of the literature as well as.

Looking at claims data et cetera, and we.

Periodically reassess. This this is a growing population and it's really a function of the.

Speaker 6: the rapid growth of the use of antipsychotics, especially in...

The rapid growth of the use of antipsychotic, especially in.

Speaker 6: non-psychotic conditions. So, if you think about it, antipsychotics are widely used to treat their adjunctive treatments in schizophrenia. They're used in bipolar. They're used to treat anxiety. There's a number of off-label uses of antipsychotics. And so, you know, we have seen that over time, as the use of antipsychotics spans, unfortunately, so does the population with TD.

Non psychotic conditions. So if you think about Amazon products are widely used to treat.

Our objective treatments in schizophrenia, there used in bipolar they used to treat anxiety theres a number of off label uses of anti psychotics. So.

We have seen that over time as the use of <unk> fans. Unfortunately, so does the population with TD.

Speaker 6: We'll continue to reassess the size of the population and, importantly, the progress that we're making in diagnosing, helping those patients get diagnosed.

We will continue to reassess the size of the population and.

Importantly, the progress, we're making in diagnosing helping those patients get diagnosed.

Speaker 6: At the beginning of our launch back in 2017, we estimated most single digit percent of those individuals had yet to be given a diagnosis. Today, we estimate about a quarter.

At the beginning of our launch.

In 2017, we estimated low single digit percent of those individuals who have yet to be given a diagnosis today, we estimate about a quarter of them have been diagnosed.

Speaker 6: have been diagnosed. Importantly, only about half of patients that get a diagnosis today are even offered a VMAT2 inhibitor.

Importantly, only about half of <unk>.

Patients that get a diagnosis today or even offered a <unk> two inhibitor. So there's a long way to go in terms of making progress with bridging the gap between the diagnosed population in the prevalent population as well as making sure that.

Speaker 6: So there's a long way to go in terms of making progress with bridging the gap between the diagnosed population and the prevalent population, as well as making sure that everyone that gets the diagnosis is offered effective treatment.

Everyone that gets the diagnosis is offered effective treatment.

Speaker 6: The last thing I'll say here is, you know, you asked about what's the goal, well the goal would be 100%, but realistically, we know that not everyone

The last thing I'll say here is you asked about what's the what's.

The goal the goal would be 100%, but realistically, we know that not everyone.

Speaker 6: that gets a disease is going to get diagnosed. But we certainly can get a lot higher.

That gets a disease is going to get diagnosed but we certainly can get a lot higher.

Speaker 6: in the coming years in terms of making sure that TD is routinely screened and diagnosed regardless of care setting.

In the coming years in terms of making sure that TD is routinely screened and diagnose regardless of care setting.

Speaker 6: And we're leveraging the APA guidelines.

And we're leveraging the API guidelines too.

Speaker 6: to really reinforce that that is the expectation and that is the standard of care for especially these patients with

Really reinforced that that is the expectation and that is the standard of care for especially these patients with <unk>.

Speaker 6: psychiatric conditions being treated with amnesticotic medicine.

Conditions being treated with MSA chronic medicines.

Great. Thank you very much.

Speaker 1: And we'll move next to Vimil Dibon with Mizzou Health Securities. Please go ahead.

And we'll move next to.

Upon.

This is <unk> securities. Please go ahead.

Great. Thanks for taking my question, maybe one just quick follow up on the last question. I think you said that the growing population I don't know if maybe you could quantify that a little bit for us just kind of how you see the overall TV market growth, but my question is actually on a pick up on.

Speaker 4: Great, thanks for taking my question. Maybe one just quick follow up on the last.

Speaker 4: question. I think you said the growing population. I don't know if maybe you could quantify that a little bit for us, just kind of how you see the overall TD market growth. But my question is actually on a pick-up phone. And I know there's a lot of synergies for that product and having your reps selling that along with Ingressa, but I'm just curious if you can give us a little more better sense when you think you may be able to get better commercial access and when you think it actually might be delivering more.

<unk>.

I know, there's a lot of synergies to that product and having your reps selling that along with the congrats.

I'm just curious if you can give us a little better sense. When you think you may be able to get better commercial actions and when do you think anything Mike on someone's going to be delivering more channels. I mean looking at consensus numbers. It does look like people are assuming a couple of hundred million dollars sales from that product alone.

Speaker 4: I mean, I'm looking at consensus numbers, it does look like people are assuming a couple hundred million in sales for that product alone, you know, out several years from now. So, I'm just trying to get a sense if you think that's realistic, or do you think that is a smaller opportunity, that's more of the synergies again, where we should see the value. Thanks.

Years from now so I'm just trying to get a sense. If you think that's realistic or should we think of that as a solid opportunity more than the synergies again.

We should see the value. Thank you.

Yes, let me let me address here.

Speaker 6: Yeah, let me let me address your question of the clarifying question about the growing population.

The question of the clarifying question about growing population.

Speaker 6: And then I'll tackle your question about agendas.

MPD and then I'll tackle your question about.

On <unk> so.

Speaker 6: So the reason I said that it's a growing population is that the use of antipsychotics continues to expand. There's been 60 million, yeah, 70, excuse me.

The reason I said that it is a growing population is that the use of anti psychotics continues to expand their spend.

<unk> million 70 excuse me.

Speaker 6: 70 million prescriptions of antipsychotics over the past year, and so, you know, that continues to expand as the uses for antipsychotics expand, and especially in this pandemic environment.

70 million prescriptions of antipsychotic, so over the past year and so.

That continues to expand as the uses for antipsychotic expand and especially in this.

<unk> environment.

Speaker 6: where more and more people are being treated for mental health disorders.

We're.

More and more people are being treated for.

Mental health disorders.

Speaker 6: So, even though second-generation antipsychotics tend to have a lower incidence of TD, the greatly expanded use of antipsychotics is what's leading to a growing TD patient population over time.

No.

Even though second generation MSA products tend to have a lower incidence of television.

The greatly expanded use of NFC products is what's leading to.

Our growing on PD patient population over time.

Speaker 6: So that, once again, is something that we, you know, continue to monitor and we update our estimates. And, you know, you might recall that five years ago, our estimate was around 500,000 people with TD. And today, we estimate it's closer to 600,000. So if you correlate TD prevalence with, you know, how quickly the antipsychotic use is going, you have the antipsychotic market is growing 3 to 5%.

So once again, it's something that we continue to monitor and we update our estimates and you might recall that five years ago. Our estimate was around 500000 people with TVN today as we estimate that it's closer to 600000, so a few correlated TB.

Prevalence with how quickly the inkjet psychotic uses is going you have you have.

The <unk> market is growing 3% to 5%, but it is growing faster than the normal general population, but it's hard to give you an exact number on.

Speaker 9: So, you know, it's growing faster than the normal general population, but it's hard to give you an exact number on, you know, what the exact percentage of patients that have TD, but it is a growing, you know, segment.

You know what the exact percentage of patients that have PD, but it is a growing segment.

Speaker 6: The other part of your question was related to on gentis and coverage. I made a point in my prepared remarks that we shouldn't expect a great acceleration.

The other part of your question was related to on Genesis and coverage.

Point in my prepared remarks that we Shouldnt expect.

Great acceleration.

Speaker 6: with the sales of Ongensis in 2022 primarily because

With the sales of <unk> in 2022, primarily because for the majority of Medicare part D plans. It remains a non formulary product.

Speaker 6: For the majority of Medicare Part D plans, it remains a non-formulary product, and I will clarify that that is a dynamic that's seen really across all branded anti-Parkinson's medicines.

We'll clarify that.

That is dynamic that's seen really across all branded any Parkinson's medicines.

Speaker 6: Especially within the Medicare plans, they tend to treat.

Especially within the Medicare plans they tend to treat.

Speaker 6: branded medicines as non-formulary products. So, you know, we'll continue to help our customers to get access through the formulary exceptions process.

Branded medicines as non formulary products so.

We will continue to help our customers to get access through the formulary exceptions process.

Speaker 6: The other thing I'll say is that we do believe that having a dedicated neurology sales team will benefit on checks.

The other thing I'll say is that we do believe that having a dedicated.

<unk> sales team will benefit on Genesis.

Speaker 6: As I mentioned earlier, it allows us to reach more neurologists and to see our highest value customers more frequently, and that would benefit both on GENXs and, of course, Ingressive Intardive Dyskinesia.

As I mentioned earlier allows us to reach more neurologists and to see our highest value customers more frequently.

And that would benefit both on <unk> and <unk>.

Of course, <unk> in tardive dyskinesia.

Okay. Thank you.

We'll move next to Marc Goodman.

Speaker 1: We'll move next to Mark Goodman with SBC Lyric. Please go ahead.

<unk> Leerink. Please go ahead.

Thanks Irene.

Speaker 5: Thanks. Irene, can you talk about why you like the selective M4 agonist? You know, just in the context, we have different companies pursuing, you know, M1 or M1, M4. I'm just curious, you know, why you like this one. And Matt, maybe could you just clarify the comments in the press release just about taxes and just so we understand what will be the, you know, the tax on the income statement versus the actual cash taxes and when these NOLs are going to run off and just how we should think about tax rate going forward. Thank you.

Can you talk about why you like the selective <unk> agonist just in the context, we have different companies pursuing one or more than four just curious why you like this one and then maybe could you just clarify the comments in the press release just about taxes.

So we understand what will be the.

No.

Some of the income statement versus the actual cash taxes.

The wells are going to run off and just how we should think about tax rate going forward.

Speaker 7: Yeah, certainly. So yeah, we're very excited about the opportunity that we have through our in-licensing from SocioHepatitis for the selective M4 agonist. And if you're correct, there are two molecules in this space that have at least in part validated clinically the M4 mechanism in the treatment of psychosis and schizophrenia. And the reason we like the molecule that we were able to acquire here is that because it is a selective direct agonist of M4, and that gives us a benefit in several ways. First of all, because it's not an ulcerative modulator, which is what one of the competitive modules in the space mechanism is, it doesn't require the substrate acetylcholine to be effective in the brain treating patients. And certainly in many indications that we might be interested in pursuing with our muscarinic portfolio, there is a deficit of acetylcholine in those patient populations. And so the likelihood of having an effective medication that requires the presence of that substrate is in question, I would say. And so with the direct agonist approach, we believe we have the potential to be investing vast opportunity against this target. And then we will be starting a clinical study in phase two in schizophrenia to understand that better later this year.

Yes, Sidney so yes, we're very excited about the opportunity that we have seen since they have tied for the selective <unk> agonist.

And you're correct there are two molecules in this space.

Leasing.

Clinically <unk> mechanism in the treatment of <unk>.

Schizophrenia.

We can we like see molecule that we were able to acquire here is that is it.

Selective direct agonist.

And so and that gives us a benefit in several ways first of all.

Because it doesn't it's not a.

Oscar modulate <unk>, which is one of the competitive amongst small businesses face mechanism is it doesn't require the substrate acetyl choline to be effective in the brain and treating patients.

And certainly in many indications that.

That we might be interested in helium muscarinic portfolio. There is adapted to democratize coding in those patient populations and so the likelihood of having an effective medications that requires the presence of that.

Great.

It's in question I would say and so with the direct agonist approach. We believe we have the potential to be a best in class opportunity.

<unk> targets.

Then we will be starting a clinical study in phase II schizophrenia to understand that better later this year.

Okay.

Sure.

Speaker 9: Yeah, so on the tax front, you know, it's always noisy when you have low book income, and your permanent items will drive different volatility in your effective tax rate. So

Yes on the tax front.

It's always noisy when you have low.

Book income.

You are permanent items will drive different.

Volatility in your effective tax rate. So I think the midterm guide that previously provided is around 24% would be effective tax rate is when everything normalizes.

Speaker 9: I think the midterm guide that I've previously provided is around 24% would be effective tax rate is when everything normalizes.

Speaker 9: On a cash tax basis, our expectation is we'll burn through the remainder of the NOLs.

On a cash tax basis, our expectation is we'll burn through the remainder of the Nols.

Speaker 9: this year. A big portion of that is just the tax legislation change.

This year.

<unk> portion of that is just the tax legislation change that causes you to have to capitalize your R&D and that then gets taken as a deduction over over time now hopefully that legislation does change.

Speaker 9: That causes you to have to capitalize your R&D, and that then gets taken as a deduction over time now. Hopefully that legislation does change, but I would just say that that's going to cause us to burn through the remainder of our NOLs this year. That then puts us in a position where we're paying federal cash tax here later this year, but it would be somewhat minimal.

But.

I would just say that that's going to cause us to burn through the remainder of our Nols. This year that then puts us in a.

Our position, where we're paying federal cash tax here later this year, but it would be somewhat minimal.

Speaker 9: So, I would say for this year, I think more guys get to a four to five percent of.

I would say for this year guide.

Got you.

4% to 5%.

Of income cash tax for speed and a little bit on the.

Speaker 9: of income cash tax for state and a little bit on the

Speaker 9: on the federal side and then next year we'll more than likely be a full cash tax payer that would be somewhat equivalent to our effective tax rate.

On the federal side, and then next year.

More than likely be a full cash taxpayer.

The somewhat equivalent to our effective tax rate.

Thanks.

Yes.

Speaker 1: And we'll move next to Charles Duncan with Cantor Fitzgerald. Please go ahead.

And next to Charles Duncan with Cantor Fitzgerald. Please go ahead.

Yes.

Speaker 13: Yeah, good morning Kevin and team congrats on weathering effectively weathering the challenges of 21.

Kevin and team congrats on weathering effectively weathering the challenges of 'twenty one.

Speaker 13: Thanks for the guide. I had two quick questions, one for Eric, one for Irie. The Eric question is related to the new Salesforce deployment you said.

For the guide I had two quick questions one for Eric one for IV. Eric question is related to the new sales force deployment you said.

Speaker 13: really in the field this month, but I guess, or by the end of the quarter, but I guess I'm wondering if you could give us a sense of the key metrics beyond revenue that you would look to to gauge that investment. And then for Ivory, I'm wondering about 104, you know, essential tremor versus CSWS, very different patient populations. And I guess I'm wondering

In the field this month, but I guess or by the end of the quarter.

I guess I'm wondering if you could give us a sense of the key metrics beyond revenue.

You would look look to to gauge that investment and then for Ivory I'm wondering about one O for essential tremor versus C. CSW as very different patient populations and I guess I'm wondering if you could provide us color on endpoints that youre looking at.

Speaker 13: you could provide us color on the endpoints that you're looking at for those proof-of-concept studies and which ones have perhaps more predictive value for clinical success over time.

For those proof of concept studies in which which ones have perhaps more predictive value for clinical success over time.

Yes, good morning Chaz.

Speaker 6: Yeah, good morning, Chad. With regards to the new the new sales team members, you know, we are going to be looking at, you know, what I'll call

With regard to the new the new sales team members.

We are going to be looking at what ill call.

Leading indicators as.

Speaker 6: leading indicators as we get out of the gate, and certainly looking to learn as we go and make adjustments, you know, going into the year. The kind of leading indicators that I'm talking about really are related to how quickly the new team members can become effective.

As we get out of the gate.

Certainly looking to.

Learn as we go and make adjustments.

Going into the year kind of leading indicators that I'm talking about really are.

Related to how quickly the new team members can become effective.

In their roles.

Speaker 6: You know, everyone that we're hiring has considerable experience, either in psychiatry, neurology, long-term care, you know, average about 15 years of sales experience. However, they haven't sold TD medication before, they haven't sold Ingreza. And so, you know, there is a little bit of a learning curve. And so some of the things that we look, you know, look at include, you know, how able they are to get in front of their key customers.

Everyone that we're hiring.

His considerable experience either in psychiatry, and neurology long term care.

On average about 15 years of sales experience. However, they haven't sold.

TD medication before they haven't sold in Gaza and so.

There is a little bit of a learning curve and so some of the things that we look look at include.

<unk>.

<unk>, how able they are to get in front of their key customers.

Speaker 6: the ability to leverage resources like peer-to-peer programs, sampling, lunchtime in-service programs, things like that. And ultimately, you know, we will be tracking effectiveness in terms of generating new patient starts.

The ability to leverage resources like peer to peer programs sampling.

Lunch time in service programs things like that.

And ultimately.

We will.

Be tracking effectiveness in terms of generating new patient starts.

Speaker 6: as a key component. There's been a lot of work that's been happening here as we've been hiring and training our new team members.

A key component there has been a lot of work that's been happening here is we've been hiring and training our new team members.

Speaker 6: to help them get off to a new start, you know, warm handoffs of existing customer relationships.

To help them get off to a new start warm handoffs of existing customer relationships doing.

Speaker 6: doing ride-alongs in the field and so on. So, you know, we're really excited about having an expanded field sales team, and we're very optimistic about the impact it's going to have, especially in the second half of the year. So, stay tuned for more as we get further into it.

Moving right along in the field and so on so.

We are really excited about having an expanded field sales team and we're very optimistic about the impact it's going to have especially in the second half of the year. So stay tuned for more as we get further into it okay.

Speaker 7: Okay, so on 104, the first thing I would say is that these are both Phase II trials, one in ET and one in CSWS. They're both adequately powered to be able to detect a signal against the primary endpoint for each trial. The primary endpoint in each of the trials, whether it's the tremor amplitude in the ET trial or the EEG endpoint in the CSWS, although they are not the clinical endpoint themselves, they are very helpful and informative with respect to the clinical impact that the medication could likely have.

Okay.

For the first thing I would say is that these are both phase II trials, one in <unk> and <unk>. They both adequately powered to be able to detect a signal again the primary endpoint for each trial the primary endpoint in each of the trials whether it makes the.

Tim amplitude in the <unk> trial, or the EEG and DSW at although they are not the clinical endpoint themselves. They are very helpful and informative with respect to the clinical impact that the medication could likely.

So also for both the <unk> trial and the <unk> trial, we do have some b clinical endpoints themselves into the trial, but obviously these are relatively short term treatment trial. So.

Speaker 7: So also for both the ET trial and the CSWS trial, we do have the clinical endpoints themselves built into the trial, but obviously these are relatively short-term treatment trials, so whilst we'll get an indication from these initial phase two trials as to the clinical impact of the medication beyond the primary endpoint, I think it would obviously require us to go into larger scale registration trials to validate that.

We will get an indication from these initial phase II trials.

Clinical impact of the medications beyond the primary endpoint I think it would.

The client has to go into larger scale that spacing pilot.

Validate that.

Hey, good helpful. Thank you.

Okay.

Okay.

And we'll move next to Chris Sheppard Tani.

Speaker 1: And we'll move next to Chris Shibutani with Goldman Sachs. Please go ahead.

Goldman Sachs. Please go ahead.

Great. Thank you two questions Irene if I could press you a little bit further on 104 there.

Speaker 11: Great, thank you. Two questions. Irie, if I could press you a little bit further on 104 there, maybe talk about what your expectations are for the placebo response in the essential tremor study. Others have observed very large placebo effects. So can you quantify what you think would be the bar to hit in terms of.

Maybe talk about what your expectations are for the placebo response in the essential tremor study others have observed very large placebo effect can you quantify what you think would be the bar to hit in terms of treatment response in terms of either perhaps percentage of patients responding or the percentage decrease in tremor amplitude.

Speaker 11: treatment response in terms of either perhaps patients responding or the percent decrease in tremor amplitude. And then the 2nd question for Matt appreciate the 1st time annual guidance. If I think back to 2021, granted an unusual period, you were helping us with fairly specific guidance on the revenue from a quarterly basis.

And then the second question for Matt I. Appreciate the first time annual guidance, if I think back to 2021 granted unusual period.

They're helping us win.

With fairly specific guidance on the revenues on a quarterly basis. So.

Speaker 11: As you have not provided commentary specifically beyond the general seasonality that this experienced group of analysts seems to have, should we interpret this to mean that you're comfortable with where consensus currently is in terms of thinking about Ingresa revenues as we progress, in particular, for the first quarter? Thank you.

As you have not provided commentary specifically beyond the general seasonality that this experienced group of analysts seems to have should we interpret this to mean that you're comfortable with where consensus currently is in terms of thinking about <unk> revenues as we progress in particular for the first quarter. Thank you.

Okay.

Speaker 7: Okay, briefly for the 104 question, I mean, obviously, there are two trials. In CSWS, that is an EEG endpoint in a very severely impacted patient population, where we would anticipate the placebo response from the EEG to be low. And I think there haven't been studies done to any great extent in that population, but for treatments that have looked at that EEG endpoint, such as steroid treatment, intimate steroid treatment, I think the placebo response we anticipate there is low. In essential tremor, it's very variable, as you said. We have designed this study in order to try to mitigate against placebo response. It's a single-site study. It's a crossover study, which allows us the power to look within a subject. And so I think we have done everything we, within our power to mitigate that response. And obviously, then, mid-year, as we get the data, we'll be able to take a look at that in the context of what we can.

Of the.

One of your question I mean, obviously there are two trials in CSW asset isn't EEG endpoint in a very severely impacted patient population, where we would anticipate that placebo response on the EEG to below and I think that Havent been studies done to any great extent in a population that.

Treatments that have looked at that EEG endpoint.

Treatment into military treatment I think thats placebo response is low.

In essential tremor.

Variable as you said, we have designed this study in order to try to mitigate against placebo response.

It looks like steady its a crossover study, which allows us to pilot and look within the sub debt and so I think we have done everything he is in a pilot to mitigate that response and obviously then midyear as we get the data we'll be able to take a look at that.

Okay.

Speaker 9: Yeah, as I said earlier, Chris, on the on the annual guide, you know, we feel comfortable with the ranges that we've provided. And I think when you look back over time, you can see this normal seasonality of sales being low 20% type range for.

Yes, as I said earlier Chris.

On the annual guide.

We feel comfortable with the ranges that we've provided and I think when.

When you look back over time, you can see there is normal seasonality.

Sales being low 20% type range for <unk>.

Speaker 9: for Q1, which really reflects somewhat of a pullback from Q4 to Q1. And then, like I said earlier, recovery into Q2. I would say the biggest dynamic outside of the environment.

For Q1, which really reflects somewhat of a pullback from Q4 to Q1 and like I said earlier recovery into into Q2, I would say the biggest dynamic outside the environment really comes down to how effective we are at keeping pace.

Speaker 9: really comes down to how effective we are at keeping.

Speaker 9: patients on treatment and how quickly they get through that reauthorization process. And as Kevin and Eric mentioned earlier, we were working very hard in Q4.

Patients on treatment and how quickly they get through that reauthorization process and as Kevin and Eric mentioned earlier, we are working very hard in Q4.

Speaker 9: to be on top of that and to improve in that regard. So I know there'd be a lot of desire for me to be more specific than what I am on Q1.

To be on top of that into to improve in that regard. So I know there'd be a lot of desire for me to be more specific than what I am on on Q1.

Speaker 9: But I think the dynamics are fairly clear.

But I think the dynamics are fairly clear hard to predict I know on the growths in that front just a clarification I think on a palm have raised.

Speaker 9: Hard to predict, I know. On the growth in that front, just a clarification, and I think Ana Palm had raised this.

Speaker 9: In Q1, you know, we would expect our net revenue per script to be around, call it 5,300, and then it will improve throughout the year as the gross net discount wanes.

In Q1, we would expect our net revenue per script to be around call. It 5300, and then it will improve throughout the year as the <unk>.

Gross to net discount Wayne coming out of the donut hole and on average we would expect our net revenue per script to be around $5400, which is similar to 2021.

Speaker 9: coming out of the donut hole and on average we would expect our net revenue per script to be around $5,400, which is similar to 2021.

Thanks.

And well move next to Evan.

Speaker 1: And we'll move next to Evan Seigerman with BMO Capital Markets. Please go ahead.

<unk> with BMO capital markets. Please go ahead.

Hi, guys. Thank you so much for taking my question. So this is not the first time you've made the discrete investment in the commercial efforts of the organization for <unk> can you remind us what the ROI was on the prior investment and what do you hope to drive from this $100 million incremental investments are there any specific metrics youre looking at here. Thank you.

Speaker 6: Hi, guys. Thank you so much for taking my question. So this is not the first time you've made the discreet investment in the commercial effort of the organization for Ingresa. Can you remind us what the ROI was on the prior investment? And what do you hope to drive from this one hundred million dollar incremental investment? Are there any specific metrics you're looking at here? Thank you.

Speaker 6: Yes, as you've noted, it's not the first investment, and frankly, it may not be the last, you know, as we move forward over the course of what's a very long lifecycle for this product. As a reminder, we launched in

Yes.

As you've noted is not the first investment.

Frankly.

It may not be the last.

We move forward over the course of what's a very.

Long lifecycle for this product as a reminder, we launched in 2015 with initial sales force excuse me 2017 with an initial sales force of.

Speaker 6: 2015 with an initial sales force, excuse me, 2017 with an initial sales force of

Speaker 6: About 140 territories quickly learned that we needed to expand the field sales force because of the rapid update that we were seeing.

About 140 territories.

Quickly learned that we needed to expand the field sales force because of the rapid uptake that we're seeing.

Speaker 6: um in frankly that exceeded our our early expectations

And frankly that exceeded our early expectations.

Speaker 6: The team that we've had in place for the last several years has been a little over 200 territories covering both neurology and psychiatry, and as we had disclosed previously,

The team that we've had in place for the last several years has been a little over 200.

Territories, covering both neurology and psychiatry.

And as we have disclosed.

Previously.

Speaker 6: In looking at where we were with the development of the market, the fact that we've made progress in raising the diagnosis rate, the fact that there are a much larger number of prescribers of Ingresa now than there were early in the launch, and frankly, a large number of high potential prescribers, we decided to pull the trigger on reorganizing and expanding our field sales team. In looking at where we were with the development of the market, the fact that we've made progress in raising the diagnosis rate, the fact that there are a much larger number of prescribers of Ingresa now than there were early in the launch, and frankly, a large number of high potential prescribers, we decided to pull the trigger on reorganizing and expanding our field sales team.

And looking at where we were with the development of the market. The fact that we have.

Made progress in <unk>.

<unk> the diagnosis rate the fact that there are much larger.

The number of prescribers of <unk> now than they were early in the launch and frankly, a large number of high potential prescribers, we've decided to pull the trigger on.

Reorganizing and expanding our field sales team.

Speaker 6: And, you know, we think that it's the right thing to do in terms of being able to accelerate growth for the brand. And it's the right thing to do in terms of being able to help people get diagnosed and effectively treated sooner. So our aspiration is to not allow any patients to suffer needlessly with TD.

And we think that it's the right thing to do in terms of being able to accelerate growth for the brand.

And it's the right thing to do in terms of being able to help people get diagnosed and effectively treated sooner. So our aspiration is to not allow any patients that suffer needlessly with TD.

Speaker 6: So going forward, you know, we will be able to provide more color in terms of how things are going with this expansion. Certainly, you know, the psychiatry segment has and will remain the largest.

So going forward we will.

We'll be able to provide more color in terms of how things are going with this expansion is certainly.

B C.

Psychiatry segment has and will remain the.

The largest.

Speaker 6: portion of our prescription volume.

A portion of our prescription volume.

Speaker 6: We feel like there's a significant opportunity to improve in neurology.

Feel like there is a significant opportunity to improve and in neurology.

Speaker 6: It's only about 20% of our of our business comes from neurology, and we think that we can grow that with additional resource. And as I mentioned earlier, LTC.

Only about 20% of our of our.

Business comes from Neurology, and we think that we can grow that with additional resource and as I mentioned earlier LTC.

Speaker 6: is essentially an untapped opportunity. So I don't know that we'll get down to providing ROI assessments, but certainly we'll provide some additional insight in terms of how our business is growing and where the sources of business are coming from as we progress in this next phase of growth.

Is essentially an untapped opportunity.

I don't know that we will get down to providing ROI assessments, but certainly we will provide some additional insight in terms of how our business is growing and where the sources of business are coming from as we progressed in this next phase of growth.

Great. Thank you.

And we'll take our last question from Jeff Hung with Morgan Stanley . Please go ahead.

Speaker 1: And we'll take our last question from Jeff Hung with Morgan Stanley . Please go ahead.

Speaker 14: Thanks, thanks for taking the question and fitting me in for. I could ask a little bit more on.

Thanks, Thanks for taking the question and sitting in for Irene if I could ask a little bit more on.

Speaker 14: I know you said that you would look at the totality of the data in central tremors, and you need to look beyond the primary endpoint, but what kind of change in amplitude at peak frequency of the postural tremor would be clinically meaningful in this patient population?

104, I know you said that you would look at the totality of the data center with farmers and you need to look beyond the primary endpoint, but what kind of change in amplitude that peak frequency of the postural termer would be clinically meaningful in this patient population.

Speaker 7: Yeah, I think, I'm not in a position to be able to answer that, I don't think there's been a direct correlation or enough work done. If you think about this field, there's nothing been approved for the treatment since 1970, and really now the only effective treatment is, you know, off-label medications that are used. So, you know, we're doing this study looking at what we believe is a very well-controlled and appropriate endpoint to assess the trauma frequency. But in addition to that, we're obviously looking at the TETRAS ratings, which are the more clinically relevant ratings in that study, that include activities of daily living. And so, you know, for this type of proof-of-concept study, I'm really interested in the totality of the data, not to forget the initial tolerability and safety that clearly is going to be critical for a treatment that can be successful in a long-run A.T.

I think.

Im not anticipating the answer that I don't think theres been a direct correlation or enough work then if you think about it feel.

Nothing's been approved treatment 1970, and really now the only effective treatment.

Off label medications.

No.

Peter.

We're doing this study looking at what we believe very well controlled and appropriate endpoint.

China frequency, but in addition to that we're looking at the Tetra ratings, which is the more clinically relevant ratings in that study that include activities stated opinion so.

This type of proof of concept study I'm really interested in the totality of the data not just to get the initial tolerability and safety that clearly is going to be critical for a treatment that can be successful.

Keith.

Speaker 14: And since you mentioned the Tetris, are there specific changes in Tetris or CGIC that would be clinically meaningful?

And since you mentioned the Texas are there specific changes in Texas, where CGI fee that would be clinically meaningful.

I mean this is the 28 patient crossover study with two week dosing for each element of the of the.

Speaker 7: I mean, this is a 28-patient crossover study with two weeks of dosing for each element of the crossover. And so, I think we'll be very pleased if we see anything in that regard. And obviously, that sets us up for further discussions and further interactions for a registration program.

Crossover so.

I don't think it will be.

Anything in that regard.

Obviously.

The discussions with the interaction so registration program.

Thank you.

And I would now like to turn the call back to Kevin Gorman for any closing remarks.

Speaker 1: And I would now like to turn the call back to Kevin Gorman for any closing remarks.

Thank you very much and thank you everyone for your attention this morning.

Speaker 5: Thank you very much and thank you everyone for your attention this morning. As you've seen and heard today, we have quite a busy year ahead of us. What I'm looking forward to this year is returning to getting aggressive to return to pre-pandemic growth levels. I think that's very important and I'm confident that we'll be able to do that. I also look at

As you've seen and heard.

<unk>.

Quite a busy year ahead of us what im looking forward to this year.

As returning to getting aggressive returned to pre pandemic.

Growth levels, I think thats very important and I am confident that we'll be able to do that.

I also look at.

Speaker 5: a very robust pipeline with 12 phase two and phase three programs.

A very robust pipeline with 12 phase II and phase III programs and Theyre going to yield multiple milestones. Both this year and next year and when we look specifically at this year, we've talked about <unk> 104 and.

Speaker 5: And they're going to yield multiple milestones, both this year and next year. And when we look specifically at this year, we've talked about NBI 104 and yielding data in both essential tremor and CSWS. We're also looking forward to the submitting the Huntington's disease SNDA.

Yielding data in both essential tremor and CSW U S. We're also looking forward to submitting the huntington's disease.

S NDA and then finally.

Speaker 5: And then finally, we are committed to finishing enrollment both in the adult and in the pediatric CAH studies, and then getting the submission ready for those two NDAs.

We are committed to finishing enrollment both in the adult and in the Pediatrics CAH studies, and then getting the submission ready.

For those.

For those two mbas.

Speaker 5: So a busy year, and as I said, the following year is going to be jammed with even more milestones.

So a busy year and as I said, the following year is going to be jammed with even more milestones.

Speaker 5: So, once again, I thank you very much for your attention today, and we're really looking forward to getting out and meeting with all of you in person throughout the year. Take care.

Once again I. Thank you very much.

For your attention today, and we're really looking forward to getting out meeting with all of you in person.

Thanks, Jeff.

Speaker 1: This does conclude today's program. Thank you for your participation. You may disconnect at any time. Have a wonderful day.

This does conclude today's program. Thank you for your participation you may disconnect at any time and have a wonderful day.

Goodbye.

Okay.

Speaker 2: That.

[music].

Okay.

[music].