Q4 2020 Neurocrine Biosciences Inc Earnings Call

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

Operator: Good day everyone and welcome to today's Neurocrine Biosciences fourth quarter and year-end 2020 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. You may register to ask a question at any time by pressing the star and 1 on your touchtone phone.

At this time all participants are in a listen only mode. Later, you will have the opportunity to ask questions. During the question and answer session you.

You May registered asks a question at any time by pressing the star and one on your Touchtone phone.

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

Operator: Please note this call may be recorded, and I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Vice President of Investor Relations, Todd Tushla. Please go ahead. Thank you, Chloe. Good afternoon, everyone.

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

Thank you Claude.

Good afternoon, everyone and thank you for joining us on our fourth quarter and full year 'twenty and 'twenty earnings call on the call today is Kevin Gorman, Our Chief Executive Officer, Matt Abernethy, Our Chief Financial Officer, I read Roberts, our Chief Medical Officer, Eric benefits, our Chief commercial officer, and Kyle Gano, our chief business development and strategy Officer.

Todd Tushla: And thank you for joining us on our fourth quarter and full year 2020 earnings call. On the call today are Kevin Gorman, our chief executive officer; Matt Abernethy, our chief financial officer; Eiry Roberts, our chief medical officer; Eric Benevich, our chief commercial officer; and Kyle Gano, our chief business development and strategy officer. 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.

Sure.

To remind everyone that during today's call, we will be making forward looking statements.

Statements are subject to certain risks and uncertainties and our actual results may differ materially and.

Encourage you to review of the risk factors discussed in our latest SEC filings. Following our prepared remarks, we will then head into Q&A, so with that I'll turn it over to Kevin Gorman.

Todd Tushla: I encourage you to review the risk factors discussed in our latest SEC filings. Following our prepared remarks, we will then head into Q&A. So with that, I'll turn it over to Kevin Gorman. Thanks, Todd. Good afternoon.

Thanks, Todd and good afternoon.

And it's good to talk to everyone again, and it's the only been about three and a half weeks I think that's a short period of time.

Kevin C. Gorman: It's good to talk to everyone again. It's only been about three and a half weeks, I think. That's a short period of time.

We were able to touch base with many of you are and at that time, we announced our top line or links and.

Kevin C. Gorman: We were able to touch base with many of you, and at that time, we announced our top line earnings. And also, as we announced those top line earnings, we told you how encouraged we were that the brand grew during a much worsening pandemic. We also talked about how we view Q1 of 2021, which we're now about a month into. Our message and our view hasn't changed since then. This Q1's rolling out like all the other first quarters.

And and and also as we announced the top out and Arlene earnings.

And I told you of how encouraged are we worried that the brand agree with the doing and much worsening pandemic.

We also talked about how we view Q1.

Of 2021, which now we're about a month and to our message and our view hasn't changed from them. This Q1 is rolling out like all of the other first quarters and the.

The first half of Q1 is being dominated by reauthorization and.

Kevin C. Gorman: The first half of Q1 is being dominated by reauthorizations for existing patients and then prior authorizations for both new patients and those who have changed insurance plans. And again, as always, this is a tale of two quarters, where the second half of the quarter is where we expect the normal pace of business to return, but obviously, as stated before, with the impact of COVID still weighing in. Now, Matt and Eric will go into more detail on the 2020 performance and our plans for 2021, but as I look back on 2020, we performed well in all facets of the business, attaining just shy of $1 billion in sales with Ingresa, launching a new brand with Gentis, effectively managing the stop and start of several of our clinical programs, and then significantly expanding our pipeline. Now, with regard to that last point, with such a robust pipeline and our continuing commitment to responsibly manage our financial and human resources, we recently made the decision to terminate the Parkinson's program with Voyager. Those resources are being redeployed to fully exploit the near and medium-term opportunities our pipeline holds.

All of our existing patients and then prior authorizations of both.

The new patients and those who have changed the insurance plans and again as always this is a tale of two quarters, where the second half of the quarter is where we expect the normal pace of business to return, but obviously of stated before with the impact of Covid still weighing and now.

And now Matt and Eric will go into more detail on the 'twenty and 'twenty performance and our plans for 'twenty and 'twenty, one, but as I look back on 'twenty and 'twenty, we performed well and all facets of the business are attaining just shy of $1 billion and sales with and grandson of launching a new brand on Gen tests.

Effectively managing the stop and start of several of our clinical programs and then significantly expanding our pipeline now with regard to that last point with such a robust pipeline.

And our continuing commitment to manage responsibly and our financial and human resources. We recently made the decision to terminate the Parkinsons program with Voyager and <unk>.

Those resources are being redeployed to fully exploit the near and medium term opportunities our pipeline holds and the details of our pipeline will be addressed by eire.

Matthew C. Abernethy: And the details of our pipeline will be addressed by Eiry. Looking ahead, we are continuing to focus on our mission of becoming the leading neuroscience company in all three disciplines, and that means neurology, neuroendocrinology, and neuropsychiatry. So with that, I'd like to turn the call over to the rest of the team, starting with Matt. Thanks, Kevin. Good afternoon, everyone. I'll make a few brief comments on our Q4 and Greser performance, expectations for Q1, and also capital allocation. During the fourth quarter, ingressive sales were $240 million and $258 million on an inventory-adjusted basis.

Looking ahead, we are continuing to focus on our mission of becoming the leading neuroscience company and all three disciplines and that means neurology neuroendocrinology and neuropsychiatry.

The commercial medicines and along with our pipeline gives us a great foundation to achieve the school.

So with that I'd like to turn the call over to the rest of the team starting with Matt.

Thanks, Kevin Good afternoon, everyone I'll make a few brief comments and our Q4 and graduate performance expectations for Q1 and also capital allocation.

During the fourth quarter and go after the sales were $240 million and $258 million and the inventory adjusted basis. We were encouraged by the Q4, new patient additions and the strong compliance rates driving inventory adjusted sequential growth, reflecting the great need that remains for patients with heart.

Matthew C. Abernethy: We were encouraged by the Q4 new patient additions and strong compliance rates driving inventory-adjusted sequential growth, reflecting the great need that remains for patients with Tardive Dyskinesia. However, although encouraged, we acknowledge COVID has an impact on the growth trajectory of the TD market, given around 50% of patient visits to psychiatrists are still being done virtually. Our goal is to be well-positioned to accelerate growth as the impact of COVID on in-person patient visits lessens. As we enter 2021, this will mark our fourth year handling the Q1 payer-related seasonal dynamics specific to a specialty product like Ingresa, including beginning-of-the-year reauthorizations and also elevated gross-to-net discounts. Similar to prior years, we expect the growth in net discount to increase from Q4 to Q1 by around 5%.

Net dyskinesia.

Although encouraged we acknowledged COVID-19 has an impact on the growth trajectory of <unk> of.

And the TD market given around 50% of patient visits of psychiatrist are still being done virtually our goal is to be well positioned to accelerate growth as the impact of COVID-19 on in person patient visits lesson.

As we enter 'twenty 'twenty, one and it's one of marker fourth year and handling the Q1 payer related seasonal dynamics specific to of specialty products and graduate inquiry.

Including the beginning of the year reauthorization and also elevated grubbs the net discounts.

The prior years, we expect the gross to net discount to increase from Q4, the Q1 by around five per cent.

In addition, we expect net revenue per script for all of 'twenty and 'twenty and wanted to be very similar to the 'twenty 'twenty the strong access for patients.

Matthew C. Abernethy: In addition, we expect net revenue per script for all of 2021 to be very similar to 2020, with strong access for patients. We remain excited about the compelling medium and long-term potential of Ingresa and will continue to adapt in the current environment. Turning to the balance sheet, we reduced our convertible debt exposure by repurchasing about 25% of debt outstanding for approximately $190 million.

We remain excited about the compelling medium and long term potential of and grabbed the and will continue to adapt and the current environment.

Turning to the balance sheet, we reduced our convertible debt exposure by repurchasing about 25 per cent of debt outstanding for approximately of $190 million.

And our ability to generate free cash flow, we exited in 'twenty and 'twenty with over $1 billion and cash, enabling us to continue to invest and long term growth.

Matthew C. Abernethy: Given our ability to generate free cash flow, we exited 2020 with over $1 billion in cash, enabling us to continue to invest in long-term growth. Our 2021 operating expense guidance reflects our capital allocation priorities focusing on maximizing the opportunity with Ingresa, as well as advancing our pipeline with the planned initiation of eight mid to late stage programs, positioning us to be a leading neuroscience company. As you saw in the release, we reversed our tax valuation allowance this quarter and will begin recording a full tax expense in our P&L for 2021 and going forward, with federal cash tax payments expected to occur sometime in 2022, based upon the around $500 million of net operating losses that we enter the year with. With that, I hand the call over to Eiry Roberts, our Chief Medical Officer. Eiry.

Our 'twenty 'twenty, one operating expense guidance reflects our capital allocation priorities, focusing on maximizing the opportunity with and browser as well as advancing our pipeline with the planned initiation of eight mid to late stage.

Program positioning us to be of leading neuroscience company.

As you saw and the release, we reversed the tax valuation allowance this quarter and we'll begin recording of full tax expense and our P&L for 'twenty and 'twenty, one and going forward with federal cash tax payments are expected to occur sometime in 'twenty and 'twenty two based upon the around $500 million of net of.

Operating losses that we entered the year with.

With that I hand, the call over to Ivory Roberts, our Chief Medical Officer.

Great.

Thank you, Matt and good afternoon, everyone.

Eiry W. Roberts: Thank you, Matt. And good afternoon, everyone. I'm happy to provide a brief update on our clinical programs, but before I begin, I must once again thank our Neurocrine teams and partners for their passion and hard work in advancing the many clinical development programs already underway and for all their ongoing diligence and investment to ensure the successful initiation of the eight new mid to late stage clinical programs planned for this year. 2020 presented us with a broad set of unprecedented challenges, and I'm proud of the progress we made across research and development, even in the face of the pandemic. Our resilience and commitment to help patients carried the day and positions us well for a foundational year in clinical development at Neurocrine as we advance and deliver on our diverse and well-balanced neuroscience-focused pipeline in the areas of neurology, psychiatry, and neuroendocr Our lead pipeline asset, Crinesafont, for the treatment of congenital adrenal hyperplasia, continues to progress through clinical development, with the single Phase III registrational study in adults currently enrolling patients globally.

I'm happy to provide a brief update on our clinical programs.

For the begin I must once again, thank God, and Neurocrine and teams and partners for their passion and hard work and advancing the many clinical development programs already underway and the all of the ongoing diligence and investment to ensure the successful initiation of the eight new mid to late stage.

A nickel programs planned for this year.

'twenty 'twenty presented us with the broad set of unprecedented challenges and.

And I'm proud of the progress we made across research and development even in the face of the pandemic.

Resilience and commitment to help patients carried the day and positions us well for foundational year and clinical development of Neurocrine as we advance and deliver on our diverse and well balanced neuroscience focused pipeline and the areas of neurology and psychiatry and neuro.

And the chronology.

Our lead pipeline asset cornice, the pond for the treatment of congenital adrenal hyperplasia continues to progress through clinical development with the single Phase III Registrational study in adults currently enrolling patients globally.

In addition, the single parallel of pediatric registration trial remains on track to initiate and the first half of this year.

Eiry W. Roberts: In addition, the single parallel pediatric registration trial remains on track to initiate in the first half of this year. We are confident, based on our interaction with regulatory agencies, key opinion leaders, payers, and patient advocates, that if successful in the current clinical trials, we can deliver a much-needed treatment alternative for patients with CAH, many of whom currently struggle to manage in the face of inadequate and outdated treatment. Looking across our pipeline, an important product attribute shared by many of our clinical candidates is the potential to benefit patients across a number of indications. This concept of a pipeline within a product is commonly displayed in the immuno-oncology setting and is perhaps best exemplified in our pipeline by valbenazine, our internally discovered VMAT2 inhibitor currently marketed under the brand name Ingresa in the U.S. for the treatment of tardive dyskinesia.

We are confident based on our interaction with regulatory agencies key opinion leaders payers and patient advocates the.

And if successful with the current clinical trials, we can deliver and much needed treatment alternative for patients with CAH, many of whom currently struggling to manage in the face of and adequate and I.

The treatment.

Looking across our pipeline and important product attribute shared by many of our clinical candidates is the potential to benefit patients across a number of indications.

This concept of of pipeline within the product is commonly displayed and the immuno oncology setting.

And is perhaps the best exemplified in our pipeline by the benzene our internally discovered the my two inhibitor currently marketed under the brand name and grocer in the U S for the treatment of tardive dyskinesia.

The most advanced additional indication under evaluation within our pipeline football benzene is chorea in Huntington's disease.

Eiry W. Roberts: The most advanced additional indication under evaluation within our pipeline for valbenazine is Korea in Huntington's disease. Top-line data from the Phase 3 ConnectHD Registration Study is anticipated in Q4 this year. Furthermore, we plan to initiate trials with valbenazine this year in two new areas of interest, with registration phase studies in both the neurological and psychiatric indications. In addition to potentially benefiting three new patient populations, we are also looking forward to expanding the geographic reach for Ingresa in Tardive Dyskinesia. Yesterday, our partner, the Mitsubishi Tanabe Pharma Corporation, reported successful top-line results from the Asia-based J-Connect Phase 3 study designed to evaluate the efficacy and safety of valbenazine in TDs, Mitsubishi Tanabe Pharma plans to submit an application for marketing authorization of Valbenazim with the Japanese Ministry of Health and Welfare this year, and has already submitted filings for marketing authorization in South Korea, Thailand, Singapore, Indonesia and Malaysia.

Top line data from the Phase III connect HD registration study is anticipated in Q4 this year.

The more we plan to initiate trials with benzene this year into new areas of interest with registration phase studies in both the neurological and psychiatric indications.

In addition to potentially benefiting three new patient populations. We are also looking forward to expanding the geographic reach for and graduate and tardive dyskinesia.

Yesterday, our partner the Mitsubishi Tanabe Pharma Corporation reported successful top line results from the Asia based J connect phase III study designed to evaluate the efficacy and safety of both benzene and T D.

Mitsubishi Tanabe pharma plans to submit an application for marketing authorization of vowel benzene with the Japanese Ministry of Health and welfare. This yeah.

And has already submitted filings from marketing authorization in South Korea, Thailand, Singapore, Indonesia and Malaysia.

Both banners and serves as a great example of of pipeline within the product with approval and one indication already and the potential for approval and three addition, additional patient populations.

Eiry W. Roberts: Valbenazine serves as a great example of a pipeline within a product with approval in one indication already and the potential for approval in three additional patient populations. Shifting gears, but on a related note, our two precision medicine epilepsy programs also have the potential to add value for patients across multiple disease states. I'll begin with NBI 827104, or 104 for short. 104 is a potent and highly selective T-type calcium channel antagonist that is currently enrolling patients in a phase 2 study for epileptic encephalopathy with continuous spike and wave during sleep.

Shifting gears, but on a related note of two precision medicine epilepsy programs and also have the potential to add value for patients across multiple disease states.

I'll begin with N B I H 271 O four O one of full for short.

One of them for a potent and highly selective T type calcium channel antagonists and is currently enrolling patients in a phase two study for epileptic encephalopathy with continuous spike and the way you during sleep.

One of the four has the potential to expand into a range of other central nervous system disease areas and we're moving forward with the initiation of a phase two study in the first of these additional neurological indications this year.

Eiry W. Roberts: 104 has the potential to expand into a range of other central nervous system disease areas, and we're moving forward with the initiation of a phase 2 study in the first of these additional neurological indications this year. Now, turning now to NBI-921352, or simply 352, our potent and highly selective NAV1.6 sodium channel inhibitor. In response to FDA feedback on our investigational new drug application in support of a Phase II clinical trial in SCN8AD patients, we are amending the study to initiate enrollment in adolescent patients with SCN8AD in the third quarter of 2021. It is our expectation that the trial population will be expanded to include younger pediatric patients as soon as the FDA has reviewed and approved additional non-clinical information. We also plan to initiate a Phase II study of 3-5-2 for the treatment of adult focal epilepsy this year.

Turning now to N V I 921352, or simply 352, a potent and highly selective NAV one six sodium channel inhibitor.

In response to FDA feedback on our investigational new drug application and supportive of the phase two clinical trial and S. C and H a D patience and we're amending the study to initiate enrollment and adolescent patients with S. Yeah, and eight a D and the third quarter of 2020.

One.

It is our expectation the the trial population will be expanded to include the younger pediatric patients as soon as the FDA has reviewed unapproved additional non clinical information.

We also plan to initiate the phase two study of 352 for the treatment of adult focal epilepsy. This year.

As a result without to precision medicine candidates one of four and 352 will have trials underway and four distinct neurological disorders. This year.

Eiry W. Roberts: As a result, with our two precision medicine candidates, 104 and 352, we'll have trials underway in four distinct neurological disorders this year. Now turning to our Lead Psychiatry Asset, NBI 1065844, the clinical portion of the Phase 2 Interact Study, evaluating 844 as a potential treatment for the negative symptoms of schizophrenia, is complete, and we look forward to sharing initial top-line data from this study later in Q1. Our partner Takeda did an outstanding job in advancing this molecule and completing the interact study on schedule in the face of the pandemic.

Now turning to our lead psychiatry asset and B I one of 658 for.

The clinical portion of the phase two interact the study evaluating eight four as a potential treatment for the negative symptoms of schizophrenia is complete and we look forward to sharing initial top line data from this study later in Q1.

The partner Takeda did an outstanding job and advancing this molecule and completing the interact study on schedule in the face of the pandemic.

And with no current FDA approved treatments available for the negative symptoms of schizophrenia, we hope that the interact day to kind of inform our path forward for the third the revaluation of N B I ate football as the potential treatment for patients suffering from the devastating impact of schizophrenia.

Eiry W. Roberts: With no current FDA-approved treatments available for the negative symptoms of schizophrenia, we hope that the Interact data can inform a path forward for the further evaluation of NBI 844 as a potential treatment for patients suffering from the devastating impact of schizophrenia. Looking back, it is remarkable, given all the uncertainty and potential roadblocks, that we've doubled our pipeline in just two years. In summary, 2021 marks a foundational year in clinical development for Neurocrine, with two significant data readouts and the initiation of eight mid- to late-stage clinical programs. With that, I'll hand it back to you, Kevin.

Looking back it is remarkable given all the uncertainty and potential roadblocks that we've doubled our pipeline and just two years and summary, 'twenty 'twenty one marks the foundational year and clinical development for Neurocrine with two significant data readouts and the initiation of eight mid to late stage clinical programs.

With that I'll hand back to you Kevin.

Thank you very much Harry So why don't we open up for questions now.

Yeah.

Absolutely at this time, if you would like task of question. Please press the star and one on your Touchtone phone if.

And he would like to withdraw yourself from the queue you May press the pound key.

Operator: Thank you very much, Eiry. So, why don't we open up for questions now? Absolutely. At this time, if you would like to ask a question, please press the star and 1 on your touchtone phone. If you would like to withdraw yourself from the queue, you may press the pound key.

And we'll take our first question from beer and Amin with Jefferies. Please go ahead.

Yeah, Hi, guys. Thanks for taking my questions, maybe just the start on and garage.

You know clearly last year of scripts grew about 30% year over year.

What should we anticipate the growth rate to be for this year.

Biren Amin: And we'll take our first question from Biren Amin. Jeffries, please go ahead. Yeah, hi, guys. Thanks for taking my questions. Maybe just to start on Ingreso.

Well, there and you know we don't give we don't give guidance. However, I think is what we said is that we're not tightly linked to.

To quote Covid, certainly COVID-19 has an impact on our business as we've said before but it's not a one day, one impact and what we look forward to and being able to get back to that kind of growth rate and and probably even beyond is a first of is and opening up oh.

Kevin C. Gorman: You know, clearly, last year, scripts grew about 30% year over year. What should we anticipate the growth rate to be for this year? Well, Barron, you know, we don't give guidance.

Kevin C. Gorman: However, I think what we said is that we're not tightly linked to quote COVID. Certainly COVID has an impact on our business, as we've said before, but it's not a one to one impact.

Of all the clinics that we go to and I think of Big step forward. There has been the the rollout of vaccines and as those become much more available.

Eric do you have anything to add.

The only other thing I would add and I think Kevin touched on this a little bit.

Kevin C. Gorman: And what we look forward to and being able to get back to that kind of growth rate and probably even beyond is further opening up of all the clinics that we go to. And I think a big step forward there has been the rollout of vaccines as those become much more available. Eric, do you have anything to add?

Is that.

You know over the course of the year and over the course of this launch.

We've seen variability in terms of growth from quarter to quarter, we're still and the like of things in terms of Q1 and.

And dealing with the seasonal payer issues, but certainly.

Certainly we expect as we go through the course of the year that we're going to see similar patterns in terms of growth rates from quarter to quarter.

Eric S. Benevich: The only other thing I would add, and I think Kevin touched on this a little bit, is that, you know, over the course of the year and over the course of this launch, we've seen variability in terms of growth from quarter to quarter. We're still in the thick of things in terms of Q1 and dealing with the seasonal payer issues. But certainly, we expect as we go through the course of the year that we're going to see similar patterns in terms of growth rates from quarter to quarter.

Okay, and then maybe if I could have one follow up given the negative schizophrenia data this quarter.

What read throughs, if any should we make on this dataset for 844 from the recent concert familiar with the <unk> D serine and and there are negative symptom study.

Hi, I can take that so we obviously saw the data from the Detroit the deserving a concept study and.

And just a couple of comments around that study obviously a few of our features that were interesting potentially leading to the outcome that was achieved the first of all obviously the dosing in that study was extremely high in terms of the dose of a quiet of the future age of D. Serine and we don't really have any idea of.

Eric S. Benevich: And then maybe if I could have one follow-up. Given the negative schizophrenia data this quarter, what read-throughs, if any, should we make on this data set for 844 from the recent concert failure with their deuterated deserine in their negative symptom study? Hi, I can take that.

Eiry W. Roberts: So we obviously saw the data from the deuterated deserine concept study and made just a couple of comments around that study. Obviously, a few features that were interesting, potentially leading to the outcome that was achieved there.

And central bioavailability of even from the higher dose and so our understanding of how much was really getting to the target to test. The hypothesis is the big question and also the study conducted entirely in the U S and and how to vary from what we saw in the top line data very hyped.

Eiry W. Roberts: First of all, obviously, the dose used in that study was extremely high in terms of the dose required of the deuterated deserine, and we don't really have any idea of central bioavailability, even from that higher dose. And so understanding how much was really getting to the target to test the hypothesis is a big question. Also, it was a study conducted entirely in the US and had a very, from what we saw in the top line data, a very high placebo response, which is not unusual in US centers in this type of environment. Incline of activity in the negative symptom treatment.

The response, and which is not unusual and U S centers in this type of environment and so we remain very confident and and I'm committed to the the NMDA hypofunction.

Hypothesis force.

Within schizophrenia.

There are several supportive elements to that the first being obviously the NMDA antagonist themselves can produce psychotic symptomatology and onto the second of which is that there are small studies with sodium benzoate and D. Serine itself that of showing positive and claim of the activity and and the negative symptom.

And treatment, we also very confident and eight full floors of the molecule and the we know we're testing that hypothesis well given the nature of the molecule the quality of the modest molecule and the translational work that was done to demonstrate a target occupancy and downstream pharmacodynamic effect. So we're very focused on you know understanding and getting hold of the data.

Eiry W. Roberts: We're also very confident in 844 as a molecule, in that we know we're testing that hypothesis well, given the nature of the molecule, the quality of the molecule, and the translational work that was done to demonstrate target occupancy and downstream pharmacodynamic effects. So we're very focused on, you know, understanding and getting hold of the data from the INTERACT study. And as a result of that, we'll be able to see. And we'll take our next question from Paul Matisse with Stifle. Please go ahead. Great, thanks so much.

From the interest study and and as a result of that will be able to see the other the only other comment I'd make is obviously the interest that ease of global study and Ah. That's I think important in this area.

And we'll take our next question from Paul Matisse with Stifel. Please go ahead.

Great. Thanks, so much I was wondering if you could give us a little bit more color on what you're seeing on and our apps to start this year and maybe kind of getting back to December and where you are right now relative to where you were in terms of pre pandemic levels last year, and then I just have one follow up thanks.

Paul Matteis: I was wondering if you could give us a little bit more color on what you're seeing on NRX to start this year and maybe kind of getting back to December and where you are right now relative to where you were in terms of pre-pandemic levels last year. And then I just have one follow-up. Thanks. Yeah, hi, Paul.

Yeah, Hi, Paul.

The way I would describe it is that we're in the second things from a Q1 perspective you.

Eric S. Benevich: The way I would describe it is that we're in the thick of things from a Q1 perspective. You know, we had a great Q1 last year. But, as Kevin said, it was a tale of two half quarters.

You know we had a great Q1 last year, but as Kevin said it was a tale of two half quarters first half of the quarter was a lot of activity in terms of focusing on continuing patients and really minimizing the impact of reauthorization requirements and.

Eric S. Benevich: First half of the quarter was a lot of activity in terms of focusing on continuing patients and really minimizing the impact of reauthorization requirements and prior authorization requirements for patients changing plans, and so on. And then in the second half of the quarter, things really picked up in terms of new patient starts, and so on. It's the same kind of pattern that's happening this year, but it's very early.

Prior authorization requirements for patients changing plans and so on and then and the second half of the quarter things really picked up in terms of new patient starts and so on.

It's the same kind of pattern and that's happening this year its very early and we're just a few weeks into the quarter.

Eric S. Benevich: We're just a few weeks into the quarter. So it'd be premature for me to comment on on what the trends look like. But obviously, we expect to have the same kind of dynamic this year, as we've seen in past years, with the added element of COVID-19. The only aspect, Paul, that I'd add is that, you know, as we've described, we're at record NRX levels entering into the pandemic, and then we saw a pretty steep fall when patients stopped flowing into the psychiatrist's office, and then we saw a bit of recovery exiting Q3 and then through Q4, but I would say that there is still a notable gap, Paul, between where we were pre-pandemic and where we are now. And as Kevin said in the last question, you know, we're doing a lot to try to minimize the impact of COVID, but likely the biggest indicator of return to growth will be patients returning back into offices, which, you know, likely looks like it will start occurring second half of the year in a more prominent way. We'll take our next question from Tazeen Ahmad with Bank of America. Please go ahead. Thank you very much. Good afternoon.

And so it'd be premature for me to comment on on what the trends look like but obviously, we expect to have the same kind of dynamic this year as we've seen and passengers.

With the added element of COVID-19.

Okay.

And then the only as of.

The only aspect Paul that I'd add is that you know as we've described we were at record of interacts levels entering into the pandemic and then we saw a pretty steep fall when a patient and stop flowing into the psychiatrist office and then we saw a bit of recovery exiting Q3, and the group Q4, but I wouldn't.

Say that there is still a notable GAAP all between where we were pre pandemic and where we are now and as Kevin said in the last question. You know, we're doing a lot to try to minimize the impact of COVID-19, but likely the biggest indicator of return to growth will be Ah patients returning back in.

And two offices, which you know likely looks like it will start occurring a second half of the year and a more prominent way.

Yeah.

And we'll take our next question from <unk> Ahmad with Bank of America. Please go ahead.

Yes.

Thank you very much and good afternoon, and thanks for taking my questions, maybe a follow up for Irene as it relates to Inc. For four can you give us a little bit more detail on why it's important Ah and these types of schizophrenia studies the house global sites as opposed to sidestep the limited and the U S.

Tazeen Ahmad: Thanks for taking my questions. Maybe a follow-up on Eiry as it relates to 844. Can you give us a little bit more detail on why it's important in these types of schizophrenia studies to have global sites as opposed to sites just limited in the U.S.? And then I have a follow-up on Ingressa. Thank you.

And then I have a follow up on and grabbed the thank you.

And I think the thanks for the question, there's quite a lot of public data and the reason is that shows that at least at certain sites within the U S. The placebo response has been quite challenging and I think having got and geographic and spread early in the program and and.

Eiry W. Roberts: Yeah, I think, thanks for the question. There's quite a lot of published data in recent years that show that, at least at certain sites within the U.S., the placebo response has been quite challenging. And I think having that geographic spread early in the program and then being able to replicate that into Phase 3 becomes important in this type of development program. I think, you know, there's lots of different reasons behind that that's hypothesized. Some are around the quality of the patient pool. Some are around the relationship between the investigator and the patient being somewhat different at some U.S. sites than elsewhere in the world. But, you know, I don't think we really fully understand that.

And then being able to replicate that into phase III becomes important and this type of a development program and I think you know there's lots of different reasons behind that that are that it's hypothesized some of us around the quality of the patient pool some of us around the relationship between the investigator and the patient being somewhat different and some U S.

Sites and elsewhere in the world and but you know I don't think we really fully understand that I think it's just a we believe it's very important to have that geographic diversity from the outset and these programs.

We'll take our next question from Josh Shimmer with Evercore.

Please go ahead of course.

Thanks for taking the question sort of previously indicated at around 20% of tardive dyskinesia patients are diagnosed half of those are treated.

And what impact do you expect the new a P of guidelines to have and in turn.

Eiry W. Roberts: I think it's just, we believe it's very important to have that geographic diversity from the outset in these programs. We'll take our next question from Josh Schimmer with Evercore. Thanks for taking the question. So you've previously indicated around 20% of tardive dyskinesia patients are diagnosed, and half of those are treated.

The increasing the treatment rate of diagnosed patients and when do you expect that to occur and then for the 80 per cent of undiagnosed tardive dyskinesia patients, where where do you see the greatest opportunity to identify them. Thanks.

Yeah. So first of all I'll say that it's a it's a welcome development to have the E. P. A put out their updated guidelines last fall.

Eric S. Benevich: What impact do you expect the new APA guidelines to have in terms of increasing the treatment rate of diagnosed patients and when do you expect that to occur? And then, for the 80% of undiagnosed tardive dyskinesia patients, where do you see the greatest opportunity to identify them? Yeah, so first of all, I'll say that it's a welcome development to have the APA put out their updated guidelines last fall. Certainly, you know, there are some important components there, such as the recommendation of VMAT2 inhibitors as first-line treatment, but also putting into context the lack of evidence to support antipsychotic adjustment as a treatment strategy for TD, and the fact that cogentin, for example, and anticho In terms of when do we expect those new guidelines to start benefiting patients with TD, well, we're already attempting to do that. We've incorporated the new guidelines into educational programming.

Certainly you know there are some important components there such as of the recommendation of the met two inhibitors as first line treatment, but also.

Putting into context, the lack of evidence to support and the psychotic adjustment as a treatment strategy for TD and.

And the fact that.

The cogent and for example.

And anticholinergic agents can actually do more harm than good and these patients and the it's been a widespread of treatment approach in the past and terms of when do we expect those new guidelines to start benefiting patients with T. D. Well, we're already attempting to do that we've incorporated the new guidelines into.

Educational programming, we've rolled them out to our field sales team our field medical team has access to those guidelines and certainly they've been incorporated into the discussions that we're having with thought leaders as well as with community providers. So that's an important dynamic and we're going to continue to make sure that.

And the psychiatry community, everyone that we'd that we talk to and work with is aware of the new recommendations from the E. P. A.

Eric S. Benevich: We've rolled them out to our field sales team. Our field medical team has access to those guidelines, and certainly, they've been incorporated into discussions that we're having with thought leaders as well as with community providers. So that's an important dynamic, and we're going to continue to make sure that in the psychiatric community, everyone that we talk to and work with is aware of the new recommendations from the APA. Then, with regard to the second half of your question, in terms of the majority of patients that still remain undiagnosed with TD and what can be done to address that situation, obviously, we've invested a lot in education, especially We're coming up on four years now since the launch of Ingress, and we feel like we've made an awful lot of progress.

And then with regards to the second half of your question in terms of the.

The majority of patients still remain undiagnosed with TD and you know what can be done to to address that situation.

We've invested a lot in education, and especially on the health care provider side.

We're coming up on four years now since the launch of of and graduate and we feel like we've made an awful lot of progress. However, there are still.

A large amount of information that you know the week and share in terms of helping providers, especially in psychiatry.

And do more confident and capable in terms of the ability to recognize and diagnose TD and we're also continuing to invest in patients and care partners.

Directly for example, and our educational efforts with the talk about TD DTC campaign, but also indirectly working through patient advocacy groups and the other venues so.

Eric S. Benevich: However, there is still a large amount of information that we can share in terms of helping providers, especially in psychiatry, to be more confident and capable in terms of their ability to recognize and diagnose TD. We're also continuing to invest in patients and care partners directly, for example, in our educational efforts with the Talk About TD DTC campaign, but also indirectly working through patient advocacy groups and other venues. We're going to continue to educate all the stakeholders, whether it's the providers, whether it's the patients, working with advocacy organizations, professional medical associations, and so on, and we'll continue to make progress there. We feel really good about the progress that we've made so far, but we recognize that there are still a lot of people suffering from TD that could benefit from it. And we'll take our next question from Laura Christensen with Cowan. Please go ahead.

You know, we're going to continue to educate all of the stakeholders, whether it's the providers whether it's the patients.

You know working with the advocacy organizations professional medical associations and so on and we'll continue to make progress.

Yes, there, but feel really good about the progress that we've made so far but we recognize that there's still a lot of people suffering from TD that could benefit from treatment.

And we'll take our next question from Laura Christianson with Cowen. Please go ahead.

Hi, Thanks for taking my question and congrats on another great quarter, and so I'm just curious on the and Qantas launch and what you're seeing so far from the physician prescribing and then also we turned from Kols that patients with Parkinson's like to avoid.

Good adjunct and treatment and I'm just curious if you of any sense of what what my.

And the inroads there that you're seeing thus far.

Sure I'll I'll take a crack at that and then maybe IRA has some comments he'd like to share.

With regards to the early early response to on Genesis and the feedback has been very favorable frankly, I mean, we've been in and launch and this launch mode for about a quarter.

Eric S. Benevich: Hi, thanks for taking my question. Congratulations on another great quarter. So I'm just curious about Junctive Launch, what you're seeing so far from physician prescribing, and then also, we've heard from KOLs that patients with Parkinson's like to avoid adjunctive treatment. And I'm just curious if you have any sense of what might help any inroads there that you're seeing thus far. I'll take a crack at that, and then maybe Eiry has some comments she'd like to share.

And we're still conducting you know what I would describe as introductory product presentations, we've been sampling quite of bit.

And we've been educating the neurology community not just about the product, but also about the reimbursement process. Since this is essentially non formulary product everywhere.

But the feedback has been very positive in terms of physicians are putting patients on our initial trial and getting.

Eric S. Benevich: With regard to the early response to Gentes, the feedback's been very favorable, frankly. I mean, we've been in this launch mode for about a quarter, and we're still conducting what I would describe as introductory product presentations. We've been sampling quite a bit, and we've been educating the neurology community not just about the product but also about the reimbursement process, since this is essentially a non-formulary product everywhere. But the feedback has been very positive in terms of physicians putting patients on the initial trial and getting, you know, strong reviews from the patients in terms of the benefit that they're getting with Ongentis. So this is one of those products where the clinical experience actually lives up to the clinical data. With regard to the second half of your question, with patients maybe not wanting to go on adjunctive treatment, you know, the reality is that the majority of patients that are out there with Parkinson's on levofopa therapy are on one or more adjunctive treatments already.

Getting the strong reviews from the patients in terms of the benefits that they're getting with on Gentiva. So this is one of those products, where the clinical experience actually lives up to the clinical data.

With regards to the second half of your question and.

With patients maybe not wanting to go on and adjunct of treatment the.

Reality is that the majority of patients that are out there with Parkinson's on levodopa. They already are on one or more adjunct of treatments already of.

About two thirds frankly of the 900000 people that are on levodopa <unk>.

On and adjunct of and so our approach has been to really position on <unk> as the go to adjunct of treatment and a product frankly that is ideally suited to optimize levodopa therapy. There are two enzymes in the periphery of that break down of levodopa before I can reach the brain and do it.

Job.

And comp is one of them and so you know we've been busy reminding neurologists about the important role of the Comped enzyme.

And as well as the clinical profile of of on Genesis and so ideally provider would consider adding ungentleness before escalating the dose of levodopa or adding.

Eric S. Benevich: About two-thirds, frankly, of the 900,000 people that are on levodopa are on an adjunctive treatment. And so, you know, our approach has been to really position Ongentis as the go-to adjunctive treatment and a product, frankly, that is ideally suited to optimize levodopa therapy. There are two enzymes in the periphery that break down levodopa before it can reach the brain and do its job, and Compt is one of them.

And the adjunct of treatment from another class that doesn't directly a boost of levodopa levels.

So like I said, it's early and the launch the feedback has been the favorable.

And you know, we're continuing to position on Genesis as of the go to early option for optimizing levodopa therapy and anything to add yeah. I mean, I would just add to what Eric said that you know and we know that patients and clinicians view levodopa is the gold standard treatment for Parkinson's disease and that the they are.

Eric S. Benevich: And so, you know, we've been busy reminding neurologists about the important role of the Compt enzyme as well as the clinical profile of Ongentis. And so, ideally, a provider would consider adding Ongentis before escalating the dose of levodopa or adding an adjunctive treatment from another class that doesn't directly boost levodopa levels. So, like I said, it's early in the launch, the feedback's been favorable, and we're continuing to position Ongentis as the go-to early option for optimizing levodopa therapy. Anything to add? Yeah, I mean, I would just add to what Eric said, that we know that patients and clinicians view levofopa as the gold standard treatment for Parkinson's disease, and that there's a lot of commitment and loyalty to levofopa treatment. Levodopa is always used with an adjunct, carbidopa, because of the fact that that it's necessary to optimize levofopa treatment and exposure.

A lot of commitment and loyalty to levodopa treatment and levodopa is always used with an object of Colorado for them because of the fact that that is necessary to optimize levodopa and treatment and exposure and so are we really believed that on gen. <unk> can continue to optimize that.

Levodopa treatment and and I think the <unk>.

Sometimes the patients get nervous about some of the other adjunct of agents in terms of side effect profile of the drug drug interaction and issues and things of that zone and so I think the labeling around on Gen. Two says the single once a day treatment and the ability to to be used.

Efficiently and effectively with levodopa and potentially reduce the number of doses of levodopa. The required by individuals as a result, I think that's that we've heard the that's very promising to clinicians and you know, we're obviously I'm, hoping that that a lot of lot of value for patients.

Eiry W. Roberts: And so, we really believe that Ongentis can continue to optimize that levodopa treatment. And I think sometimes patients get nervous about some of the other adjunctive agents in terms of side effect profile, drug-drug interaction, safety, and things of that sort. And so, I think the labeling around Ongentis as a single, once-a-day treatment and the ability to be used very efficiently and effectively with levodopa and potentially reduce the number of doses of levodopa required by individuals as a result, I think that we've heard that that is very promising to clinicians, and we're obviously hoping that that will add a lot of value for patients. Now, we Please go ahead.

We'll take our next question from Brian <unk> with Baird. Please go ahead.

Hey, good afternoon, guys. Thanks for taking the question and Todd I loved the smoothed jazz hold music.

On the on the prelude to the call, but you did promise me from Jan our metallic ores and one of these days and I really do want to hear that.

And my question is on of 352, and and and the plans and S. N. A E D disorders, and I guess I know, maybe it's a little premature but can you kind of talk walk us through sort of the patient population and and how you kind of think of the trial design, because it's going to be sort of like the 28 day looking primarily at.

Brian P. Skorney: Hey, good afternoon, guys. Thanks for taking the question. Todd, I love the smooth jazz hold music during the prelude to the call, but you did promise me some JNR Metallica, so one of these days I really do want to hear that.

The reduction in seizures type endpoint and and you know what are sort of like the baseline characteristics and sort of in terms of she sees the seizure frequency.

Todd Tushla: My question is on 352 and the plans for FCNAAD disorders. I guess maybe it's a little premature, but can you kind of walk us through sort of this patient population and how you kind of think of trial design? Is this going to be, you know, sort of like a 28-day looking primarily at reduction in seizures type endpoint? And, you know, what are the baseline characteristics in terms of seizure frequency in these patients where you can sort of start gauging what would be successful here?

In these patients. So you can sort of start gauging what are what would be successful here.

Yeah, we haven't really talked a great deal about the trial design up to this point and in fact, you know I think our usual and intent is to do that when the when the trial is it's posted on Clinicaltrials, Gov, which will be and <unk>.

And later this year and what I would say, though is that given that this is a very rare pediatric epilepsy and actually has you know quite heterogeneous and phenotype in terms of its of how it expresses itself in terms of seat seizure type seizure frequency.

Eiry W. Roberts: Yeah, we haven't really talked a great deal about the trial design up to this point. And in fact, you know, I think our usual intent is to do that when the trial is posted on clinicaltrials.gov, which will be, you know, later this year. What I would say, though, is that given that this is a very rare pediatric epilepsy and actually has, you know, quite a heterogeneous phenotype in terms of how it expresses itself in terms of seizure type, seizure frequency, but actually, it can be very devastating, as you may know, for patients at a very young age.

And but actually it can be very devastating as you may know for patients.

From a very young age are the important thing for us was to ensure and our interactions with the agency. The every single patient that we enrolled and this pain and this program would count towards the ability for us to bring this to patients and register of the medication and so the way in which the trial will be designed to enable us to have the best opportunity of it being a registration.

And quality trial, and and we're working through that even in the context of starting and the old the adolescent population and then moving ultimately into pediatrics, where obviously, a large amount of the value will be and derived.

Eiry W. Roberts: The important thing for us was to ensure in our interactions with the agency that every single patient that we enrolled in this program would count towards the ability for us to bring this to patients and register the medication. And so the way in which the trial will be designed is to enable us to have the best opportunity of being a registration quality trial. And we're working through that even in the context of starting in the older adolescent population and then moving ultimately into pediatrics, where obviously a large amount of the value will be derived. And we'll take our next question from Ami Fadia, Tazeen Ahmad, Anupam Rama, J.P. Morgan, Hey guys, this is Tess Ahn for Anupam.

And we'll take our next question from a new Palm Rama with J P. Morgan. Please go ahead.

Hey, guys. This is cash arms on the palm Thanks for taking the question.

And I don't think schizophrenia program.

Maybe one for Irene are you able to quantify.

Yeah.

A test you use and we only heard the first part of asking about the schizophrenia program. Then we lost you.

Can you hear me now yeah, I can hear you now.

Okay. I'm wondering if you can quantify what placebo adjusted decline on a point basis or per cent Beecher and.

And the negative subscale of the pants.

It's viewed as clinically meaningful.

And so embedded and the question is how we should be thinking about placebo performance and then is there any color you can provide on what the anticipated.

Tess Ahn: Thanks for taking the question. On the schizophrenia program... and maybe one for Eiry, are you able? Hey Tess, we only heard the first part of your question about the schizophrenia program, then we lost you. Can you hear me now?

The painted baseline range might be given the inclusion exclusion criteria yeah. Thank you so much.

Yeah, we haven't really commented the to any great extent on the the actual baseline characteristics that we anticipate I think we're going to wait to see the data and then we'll be obviously very happy to talk through the what we're seeing there are in terms of the kind of just guiding you around placebo adjusted changes and levels of clear.

Tess Ahn: Yeah, I can hear you now. Okay, I'm wondering if you can quantify what placebo-adjusted decline on a points basis or a percent basis in the negative subscale of the PANS is viewed as clinically meaningful. So embedded in the question is how we should be thinking about placebo performance. And then, is there any color you can provide on what the anticipated baseline range might be given the inclusion and exclusion criteria? Thanks so much.

Of course significance I think we all this is a very well powered trial and the in order for us to to determine of clinically significant difference of the exists and and also I would look to other positive programs in this field and so you kind of guide in terms of what the nature of that change might be the one thing I do want to make though is that although the.

Eiry W. Roberts: Yeah, we haven't really commented to any great extent on the actual baseline characteristics that we anticipate. I think we're going to wait to see the data, and then we'll obviously be very happy to talk through what we are seeing there. In terms of kind of just guiding you around placebo-adjusted changes and levels of clinical significance, I think this is a very well-powered trial in order for us to determine a clinically significant difference if one exists.

The primary end point here is the negative effect of symptom score and you know we all have a significant number of other endpoints in the study that are focused both on the negative symptoms. The total pan score and on functional and near the cognitive endpoints and you know this is the phase two dose finding study so we.

We'll be looking at the totality of the data rather than just that the primary of them find itself in order to help inform us and the next steps and development.

Eiry W. Roberts: And also, I would look to other positive programs in this field as a kind of guide in terms of what the nature of that change might be. The one point I do want to make, though, is that although the primary endpoint here is the negative factor symptom score, we have a significant number of other endpoints in this study that are focused both on the negative symptoms, the total PAN score, and on functional and cognitive endpoints. And this is a phase two dose-finding study, so we will be looking at the totality of the data rather than just at the primary endpoint itself in order to help inform us about the next steps in development. Next question from Paul Choi with Goldman Sachs; please go ahead. Thank you, and good afternoon, and thank you for taking our questions.

Take our next question from Paul Choi with Goldman Sachs. Please go ahead.

Yeah.

Thank you and good afternoon, and thank you for taking our questions on.

And another one for other players.

Please.

For and the schizophrenia trial.

Think about the dosing.

Is that you are using and and this trial you know how do you think about the sort of magnitude and therapeutic window share given the the wide wide range of doses Youre doing and just you know how do you think about a potential of dose response here and then as a follow up thanks for the Opex guidance, but I wanted to ask either Kevin or Matt as you think about the the rate of reinvestment.

And the business here is this sort of the and so you think about the longer term the right up the reinvestment and the business you'd want to continue up or how do you think about.

Thinking about generating leverage and reallocating and the increasing portion of your cash flow to the business development. Thank you very much.

Paul Choi: Another one for Eiry, please, on 844 and the schizophrenia trial: as we think about the dosing ranges that you are using in this trial, you know, how do you think about the sort of magnitude and therapeutic window here, given the wide, wide range of doses you're doing? And just, you know, how do you think about, you know, a potential dose response here? And then as a follow-up, thanks for the OPEX guidance, but I want to ask either Kevin or Matt, as you think about the rate of reinvestment into business here, is this sort of the rate of reinvestment into business you'd want to, you know, continue at, or how do you think about, you know, thinking about generating leverage and reallocating, you know, an increasing portion of your cash flow to business development?

Thanks on the first question around dose response, and Yeah, I think I've mentioned this before but in the context of this molecule April for one of the things that was really appealing to US was the really great translational medicine work that Takeda had done and as part of that they had taken of really good look at it.

Bose your response in terms of target engagement and downstream pharmacodynamic activity and so we know that the dose range that we're testing in the interact study is one which encompasses a broad range of different levels of D. A L inhibition and that's really important we believe.

And in order for us to be able to determine from of as we look at the overall benefit risk profile from the attract study, which dose or doses to progress forward with if we're successful Matt do you want to talk about the allocation of capital.

Eiry W. Roberts: Thanks. On the first question around dose response, and I think I've mentioned this before, but in the context of this molecule 844, one of the things that was really appealing to us was the really great translational medicine work that Takeda had done. And as part of that, they took a really good look at exposure response in terms of target engagement and downstream pharmacodynamic activity. And so we know that the dose range that we're testing in the InterACT study is one that encompasses a broad range of different levels of DAO inhibition. And that's really important, we believe, in order for us to be able to determine, as we look at the overall benefit-risk profile from the InterACT study, which dose or doses to progress forward with if we're successful. Matt, do you want to talk about the allocation of capital? Yeah, sure.

Yeah sure so from a rate of reinvestment perspective, Paul I would say we're more.

Focused on what do we have and hand, and how are we going to invest behind that to maximize the opportunity. We've long said, we're not going to just spend money to avoid profitability, but where we have conviction, we're going to reinvest.

Back into the business and graduate first and then the pipeline. So what I would say Paul is this is just the reflection of where we're at today, but Kyle has $1 billion of cash to work with its walls of our balance sheet and equity value and as we see the right kinds of opportunities will continue.

The b be aggressive we want to build a leading net.

<unk> Science company and I.

It's gonna take internal development and then its also going to continue to reach and on the external side. So I wouldn't say, our our opex guidance. This year is a reflection, but we do know over the long run you know reinvestment of 25 to 35 per cent of revenue back into R&D.

Matthew C. Abernethy: So from a rate of reinvestment perspective, Paul, I would say we're more focused on what we have in hand and how are we going to invest behind that to maximize the opportunity? We've long said we're not going to just spend money to avoid profitability, but where we have conviction, we're going to reinvest back into the business in Greza first and then our pipeline. So what I would say, Paul, is this is just a reflection of where we are today. But Kyle has a billion dollars of cash to work with, as well as our balance sheet and equity value.

Seems to be.

<unk> level of reinvestment for companies to have sort of sustainable.

The staying power within within biotech and that's more of a mature base. So hopefully that answers your question.

Two Jeff hung with Morgan Stanley. Please go ahead.

Thanks for taking the question for the time being you decided to maintain the partnership with boys you're on the free <unk> Ataxia gene replacement program are there differences from 18 17 that gives you confidence and friedrichs ataxia and and more broadly does that mean that you're still open to gene therapy of the modality for neuroscience for future programs.

Matthew C. Abernethy: And as we see the right kinds of opportunities, we'll continue to be aggressive. We want to build a leading neuroscience company. And I think it's going to take internal development, and then it's also going to continue to reach out on the external side. So I wouldn't say our off X guidance this year is a reflection. But we do know that in the long run, reinvestment of 25 to 35% of revenue back into R&D seems to be the right level of reinvestment for companies to have sort of sustainable, you know, staying power within biotech. And that's more of a mature base.

Yeah. Thanks for the question of where we're and as we've said from the beginning.

We're very open to gene therapy, and we said that this is just the our collaboration with Voyager is the first that will be doing and gene therapies.

And there were four programs when we started this collaboration with Voyager there as the Parkinson's program with the Y a D. C. There's a preclinical freeze ex the taxi of program and then there are two genes that we brought into the collaboration.

To work with with Voyager and so and just with all of the programs in our.

And our wholly owned pipeline.

And with and those with our collaborators each program stands independently and that collaboration with Voyager and so we look at each one of them independently and and based on their merits of the data that's being derived.

Matthew C. Abernethy: So hopefully, that answers your question, to Jeff Hung with Morgan Stanley. Thanks for taking the question. For the time being, you've decided to maintain the partnership with Voyager on the Friedrichs ataxia gene replacement program. Are there differences from 1817 that give you confidence in Friedrichs ataxia? And more broadly, does that mean that you're still open to gene therapy as a modality for neuroscience for future programs? Thanks.

And we will we will take forward invest or not and in each of those so it's there's nothing different within the Voyager collaboration and there is within the rest of our pipeline.

Yeah.

Moving next to Marc Goodman with SVP Leerink. Please go ahead.

And it looks like Mark the true his question well move next to the mill the born with Mizuho Securities. Please go ahead.

Great. Thanks, so much for taking my question.

So maybe if I could just ask again on the first quarter of sort of dynamics, a little bit more I think last year at this time and he had sort of similar commentary kind of yeah.

Kevin C. Gorman: Yeah, thanks for the question. We're, as we said from the beginning, we're very open to gene therapy, and we said that this is just our collaboration with Voyager is the first that we'll be doing in gene therapies. So there's nothing different within the Voyager collaboration than there is within the rest of our pipeline. Next to Mark Goodman with SVB leering, please go ahead.

And against the both the dynamics and then you ended up sort of deal.

During the quarter.

A little bit from the fourth quarter. It was in 2019 and so I'm just.

Kind of get a sense, Kevin and I'm sure we're going to go out of the question over the next few weeks and they go through the quarter here is that sort of performance you know sort.

The flat maybe up a little bit from fourth quarter, taking out any inventory fluctuation and sort of what are you.

Kevin C. Gorman: Vamil Devon with Mizzou House Securities, please go ahead. Great, thanks so much for taking my question. So maybe if I could just ask, again, about the first quarter's sort of dynamics a little bit more. I think last year, this time, you had sort of similar commentary, kind of, you know, warning us about the dynamics. And then you ended up sort of delivering a quarter that was up a little bit from what the fourth quarter was in 2019. And so I'm just trying to get a sense, and I'm sure we're going to get a lot of questions over the next few weeks as we go through the quarter here, is that sort of performance, you know, sort of live, maybe up a little bit from the fourth quarter, taking out any inventory fluctuations or what I know you don't give guidance.

And it would be a reasonable sort of performance I know you don't give guidance I'm just trying to get a sense of what your sort of general expectations would be and what have you.

Sort of be happy with just so we can frame it appropriately.

I'll take the true.

So we see lots of them.

Okay.

Yeah, I'm not I'm not sure that I totally understand your question, but I'll take a crack at it I mean, what we've seen really since I'm. The first full year of the launch back in 2018.

Was that.

You know and Q1.

And grocery I had to go through a process you know given the fact that it's a specialty product had to go through the process of our existing patients of I'm getting them reauthorized and.

And back on treatment and.

Each year, we've gotten a little bit better as a company and as it has the team in terms of helping our customers to navigate that process. So this is not unique to and browser and it's just a function of the fact that it's the specialty medicine.

Vamil Devon: I'm just trying to get a sense of what your sort of general expectations would be or what you'd sort of be happy with, just so we can frame it appropriately. Yeah, I'm not sure that I totally understand your question, but I'll take a crack at it. I mean, what we've seen really since the first full year of the launch back in 2018, you know in Q1. Ingressa had to go through a process, you know, given the fact that it's a specialty product, had to go through a process for existing patients of getting them reauthorized and back on treatment. And each year, we've gotten a little bit better as a company and as a team in terms of helping our customers to navigate that process. So this is not unique to Ingreso.

But as our base of patients has grown each year, you've got a larger group of patients that are at risk of dropping.

Dropping off treatment, albeit temporarily because of insurance reasons and so you know what we've seen each year is that the Q1 is challenging in terms of navigating of those those payer issues are and then we get back into a more of a growth mode. As we exited the quarter and go into Q2.

And you've seen that in years past with the strong.

The new patient starts going from Q1 to Q2, and that's frankly, what we saw in 2020, we had a record number of new patient starts and in Q1 of 2020 and.

Eric S. Benevich: It's just a function of the fact that it's a specialty medicine. But as our base of patients has grown each year, you've got a larger group of patients that are at risk of dropping off treatment, albeit temporarily, because of insurance reasons. And so, you know, what we've seen each year is that Q1 is challenging in terms of navigating those payer issues, and then we get back into more of a growth mode as we exit the quarter and go into Q2. And you've seen that in years past with strong new patient starts going from Q1 to Q2. And that's, frankly, what we saw in 2020. We had a record number of new patient starts in Q1 of 2020. And then the pandemic hit.

And then the pandemic hit.

And so from Ey.

Sort of annual cycle basis, I wouldn't expect that 'twenty 'twenty, one and it's going to look similar to years past with a challenging Q1.

Strong relatively stronger Q2, we've seen Q3 be a more challenging quarter in years past and then.

Stronger growth in Q4, so that pattern and I don't think of is going to necessarily change.

But you know with the pandemic layered on top of of everything that's created some new challenges for us in the near term.

And then the longer term obviously, we're we're very optimistic about the potential for and graduate to help many more thousands of patients.

So to build a bit on what Eric just commented on if you recall last year as you pointed out.

The overall sales were call it flattish.

Eric S. Benevich: And so, on a sort of annual cycle basis, I would expect that 2021 is going to look similar to years past with challenging Q1 and relatively stronger Q2. We've seen Q3 be a more challenging quarter in years past, and then stronger growth in Q4. So to build a bit on what Eric just commented on, if you recall last year, as you pointed out, our overall sales were call it flattish from Q4 to Q1 when adjusting for inventory.

From Q4, the Q1 when adjusting for inventories. So the same dynamics are still up play.

You mentioned this year the only other piece would be.

The fact that Covid does have an impact on the.

And our access we've spoken about earlier and this and this call.

And importantly.

As Eric said, we're working to get patients through the reauthorization process and importantly, ensuring that patients don't does continue.

Matthew C. Abernethy: So the same dynamics are still at play, as you mentioned this year. The only other piece would be the fact that COVID does have an impact on Enterax, as we've spoken about earlier in this call. But, you know, importantly, as Eric said, we're working to get patients through the reauthorization process and, importantly, ensuring that patients don't discontinue through the first quarter because that really sets us up nicely for a strong Q2 and beyond. Hey guys, this is Yatin Suneja with Guggenheim Partners. Please go ahead.

Through the through the first quarter, because that really sets us up nicely for a strong Q2 and beyond.

Ooh and Ah yeah. So.

So NASA with Guggenheim Partners. Please go ahead.

Hey, guys. This is yet and thank you for taking my question just a question on in garage are in the long run.

Once we ought to Covid. So if we look back 2018 2019 of them I think in terms of quarter over quarter script growth, but then you were growing somewhere around.

The 35 to 4500, obviously COVID-19 had a big impact in 'twenty and 'twenty, so the quarter over quarter growth decline I mean, maybe talk about conceptually like how is 2018 2019 of good proxy for our longer term from from.

Yatin Suneja: Thank you for taking my question. Just a question on Ingressa in the long run once we are through COVID. So if we look back on 2018, 2019, I think in terms of, and we have a few more questions. So, I think you were talking about quarter over quarter script growth. I think you were growing somewhere around 35 to 4500. Obviously, COVID had a big impact in 2020. So, the quarter over quarter growth declined. Maybe we could talk about conceptually, like how is 2018, 2019 a good proxy for the longer term from a growth perspective? So, I think you were growing somewhere around 35 to 4500.

The growth perspective.

Hard to say I mean, obviously, our goal and the near term is to get back onto a stronger growth trajectory and you know what we've described as the drivers for that obviously there needs to be.

Higher foot traffic into especially psychiatry practices, you know, we've we've seen that.

The G is relatively less impacted by COVID-19 than psychiatry, we've made a concerted effort.

To push more into neurology, especially with the launch of on Genesis.

The benefit and grocer.

Eric S. Benevich: Obviously, COVID had a big impact in 2020, so the quarter over quarter growth declined. Maybe talk about conceptually, like how is 2018, 2019 a good proxy for the longer term from a growth perspective? Hard to say. I mean, obviously, our goal in the near term is to get back onto a stronger growth trajectory. And you know, what we've described as drivers for that, obviously, there needs to be. We've seen that neurology is relatively less impacted by COVID than psychiatry. We've made a concerted effort to push more into neurology, especially with the launch of Ongentis to benefit Ingresa, and I think that those are going to be important drivers to help us return to stronger growth that is still relatively undeveloped. In fact, in my career in this industry, I've never worked in a therapeutic area that was less developed.

And you know I think that those are going to be important drivers to help us return to a stronger growth trajectory of with our and graduate franchise I mean, the way that I'm thinking about this is that we're still relatively early and the overall commercialization ramp for this product. This is a nascent market.

It's still relatively undeveloped and fact and my and my career in this industry I've never worked and the therapeutic area that was less developed.

And so we've got obviously, a very strong focus on recognition and diagnosis and diagnosis as a driver of of new patient starts frame browser. So you know.

And we're going to continue to do everything we can to navigate the pandemic both in terms of our ability to get in front of of our providers and psychiatry and neurology and person.

And also to leverage new approaches to helping our customers recognize and diagnose TD during.

During telehealth interactions.

And as I mentioned earlier, we're going to continue to invest in direct to consumer efforts and all of those things together will.

Eric S. Benevich: And so we've got obviously a very strong focus on recognition and diagnosis, and Diagnosis is a driver of new patient starts for Ingresa. So, you know, we're gonna continue to do everything we can to navigate the pandemic, both in terms of our ability to get in front of providers in psychiatry and neurology in person, and also to leverage new approaches to helping our customers recognize and diagnose TD during tele And as I mentioned earlier, we're going to continue to invest in direct-to-consumer efforts. And all of those things together will position us well once the pandemic starts to wane, and we see a return to normalcy in the health system. So what the quarter-over-quarter growth looks like as we go forward remains to be seen, but we're very confident in our ability to get on to a more robust growth trajectory as we move forward. Question from Joseph Stringer with Needham & Company; please go ahead. Hi, thanks for taking our questions here. A couple quick ones.

Will position us well once the pandemic starts to wane and.

And we see a return to normalcy in the and the health and the health system. So.

The quarter over crossed the.

Quarter over quarter growth looks like as we go forward and remains to be seen.

But we're very confident and our ability to to get onto a more robust growth trajectory as we move forward.

A question from Joseph Stringer with Needham and company. Please go ahead.

Hi, and thanks for taking the questions.

Questions here a couple quick ones can you comment on of the diagnose TD patients what.

Per cent of Rguest penetration, you think you currently out with and Brad.

And a follow up on the on the percentage of virtual patient she commented.

Around 50% now, but can you maybe walk us through where that was sort of at the start of the pandemic and the way.

And so where it is now and then also what percent.

Yeah.

I'd like to see or think of it will be towards the end of this year.

Okay. So I'm going to put on my Prognosticator hat here I'll I'll take your first question or your second question first with regards to what telehealth looked like pre pandemic, what it looks like now and maybe where it's headed.

Joseph Stringer: Can you comment on, of the diagnosed TD patients, what percent market penetration do you think you're currently at with Ingresa? And follow up on the percentage of virtual patients. You said it was around 50% now, but can you maybe walk us through where that was sort of at the start of the pandemic and to where it is now? And also, what percent do you think it will be towards the end of this year?

Pre pre pandemic it was a relatively.

Underutilized and I will say, though that it was more broadly utilized and psychiatry than in other therapeutic areas. You know when we launched and growth that we took a look at our telehealth and the opportunity and psychiatry and at that time.

Eric S. Benevich: Thanks. Okay, so I'm going to put on my prognosticator hat here. I'll take your first question or your second question first with regard to what telehealth looked like pre-pandemic, what it looks like now, and maybe where it's headed. Pre-pandemic, it was relatively underutilized, and I will say, though, that it was more broadly utilized in psychiatry than in other therapeutic areas. You know, when we launched Ingreso, we took a look at telehealth and the opportunity in psychiatry, and at that time, about less than 6% of all patient visits were billed as a telehealth visit. So it gives you sort of a point of reference.

Less than 6% of all of patient visits were billed as a telehealth visit. So it gives you a sort of of point of reference.

Early in the and the pandemic when states, we're issuing shelter and place directives clinics were shutting down and so on.

It got above 90% really across multiple different physician specialties and that includes both psychiatry and neurology.

And urology has bounced back to a more normal cadence over.

Over the you know over the last quarter or so.

Total patient visits are similar to what they were pre pandemic and the percentage of telehealth is less and 10% and neurology.

Eric S. Benevich: Early in the pandemic, when states were issuing shelter-in-place directives, clinics were shutting down, and so on, it got above 90%, really, across multiple different physician specialties, and that includes both psychiatry and neurology. Neurology has bounced back to a more normal cadence over the last quarter or so. Total patient visits are similar to what they were pre-pandemic, and the percentage of telehealth is less than 10% in neurology.

I'll contrast that with psychiatry psychiatry is only about 70% of the volume of patient visits of what it was pre pandemic.

And about half of all.

And of those visits are billed as telehealth.

And it may be even higher in the subset of psychiatrists that we call on with the you know and within especially Kimberly and committee of mental health and practices. So I'm quite of bit of difference in terms of the use of a telehealth between psychiatry and neurology in terms of where it's going.

Eric S. Benevich: I'll contrast that with psychiatry. Psychiatry is only about 70% of the volume of patient visits it was pre-pandemic, and about half of all of those visits are billed as telehealth. And it may be even higher in the subset of psychiatrists that we call on within, especially, community mental health practices. So quite a bit of difference in terms of the use of telehealth between psychiatry and neurology in terms of where it's going. The Biden administration recently announced that they were going to carry forward the public health emergency designation through the end of this year, which functionally means that the temporary waivers that CMS issued last year that spurred the increase in telehealth will carry forward through the balance of this year.

The by the administration and recently announced that they were going to carry.

Carry forward the public health emergency designation through the end of this year, which.

Which functionally means that the temporary waivers that CMS issued last year debt.

Spurred the increase and telehealth will carry forward through the balance of this year. So our expectation is that we're going to see a continued high levels of telehealth and psychiatry.

And then as we get further into the year you know, we can reevaluate to the extent debt psychiatrists are coming back into their practices and they're seeing their patients in person and that's why we've invested so heavily.

Eric S. Benevich: So our expectation is that we're going to see continued high levels of telehealth in psychiatry. And then, as we get further into the year, we can reevaluate the extent to which psychiatrists are coming back into their practices, and they're seeing their patients in person. That's why we've invested so heavily in telehealth. Oh, and the first part of your question, sorry, was really around the rate of diagnosis and what we're seeing there. So, obviously, you know, we see a lot of upside potential here with the majority of patients remaining as yet undiagnosed with TD. But another area of focus and opportunity for us is that, to this day, about half of the patients that do get diagnosed with TB aren't offered a VMAT2 inhibitor, and as I mentioned earlier, the APA guidelines will help to change that paradigm or that behavior in the provider community.

And telehealth.

Oh and the first part of your question sorry was really around the the rate of diagnosis and what we're seeing there. So obviously you know we see a lot of upside potential here with the majority of patients remaining as yet and <unk>.

Diagnosed with TD.

But another area of focus and opportunity for US is that to this day about half of the patients that do get diagnosed with TD arent offered of the met two inhibitor and and as I mentioned earlier the E. P. A guidelines will help to change that that paradigm or that the behavior and the and the provider.

Immunity.

So it's both a combination of increasing the rate of diagnosis and increasing that of bell available patient pool.

But also changing those practice patterns and getting physicians to recognize the beam at two inhibitors, and especially and gradual.

Eric S. Benevich: So it's both a combination of increasing the rate of diagnosis and increasing that available patient pool, but also changing those practice patterns and getting physicians to recognize that VMAT2 inhibitors, and especially Ingresa, should be considered first-line therapy. I think our next question is from Charles Duncan with Cantor Fitzgerald. Please go ahead. OK, thanks. Hi Kevin and team.

Be considered first line therapy.

And we'll take our next question from Charles Duncan with Cantor Fitzgerald. Please go ahead.

Okay, Thanks, Hi, Kevin and team. Thanks for taking the question and a question on Bell benzene and its future.

It's it's a two part question one is how the differentiate del <unk> from <unk> given some of the work that Youre doing in Korea, and then also the neuro and psych indications youre contemplating, especially given some of the kind of debate that we had a few years ago when auspex.

Charles Duncan: Thanks for taking the question. I had a question on Velbenazine and its future. It's a two-part question. One is how to differentiate Velbenazine from Ingresa given some of the work that you're doing in Korea and then also the neuro and psych indications you're contemplating, especially given some of the kind of debate that we had a few years ago when Auspex was public and Ostida was coming to the market.

Well it is public and OS data was coming to the market and then the second part is regarding Mitsubishi Tanabe collaboration congrats on the data recently I'm wondering if you could remind us of the milestones and royalty rate and any color on the patient population and Asia relative to the state.

Eiry W. Roberts: And the second part is regarding the Mitsubishi Tanabe collaboration. Congratulations on the data recently. Wondering if you could remind us of the milestones and royalty rate in any color for the patient population in Asia relative to the States. Thanks.

Matter of Kyle you want to talk about the TPC and financials.

The first.

Kyle Gano: Matt or Kyle, do you want to talk about the MTPC financials first? If Matt's not jumping on the line here, we do get a milestone for submission in the Japanese territory or in Japan, and upon approval, those are probably the most meaningful ones, and those are about $30 million in total between now and approval. And then, in terms of royalties, it's tiered on net sales between the mid teens and the mid 20s in terms of percentage. Thanks, Carolyn. Yeah, and we would guide on the royalty front to somewhere in the mid team. Eiry, do you want to take the first part of Chaz's question? Yes, certainly, Chaz. So, with respect to Huntington's career and the valbenazine program and potential differentiation from other VMAT2 inhibitors already approved in that space, if I understand your question correctly, I mean, obviously, we're very confident in the profile that we've seen and its differentiation in tardive dyskinesia, and a lot of that revolves around the simple once-a-day treatment paradigm, continuing with the once-a-day treatment paradigm.

If the math jumping on the line here, we do get a milestone for our submission.

Submission and the Japanese territory or in Japan, and upon approval of is probably the most meaningful ones.

And of those those are.

About $30 million and total.

Waned at all and approval.

And then in terms of the royalties, it's a tiered on net sales and the mid teens to mid twenties and in terms of percentage.

Thanks Colin.

Yeah, and we would guide on the royalty of front to.

It's somewhere in the mid teens.

Right I read you want to take the first part of <unk> question, Yes, Sydney and jazz and so with respect to our Huntington's chorea and the Val benzene program and potential differentiation from other beam out two inhibitors already approved and not a space. If I understand your question correctly I mean, obviously.

We're very confident and the profile that we've seen and its differentiation and tardive dyskinesia and and a lot of that revolves around the simple once a day treatment paradigm. The lack of the need for complex titration, and a very favorable benefit risk profile and tardive dyskinesia and so on.

And the mm connect HD trial is designed to replicate that as much as possible and this new population and so we hope to be able to deliver on a very favorable benefit risk profile and that population and continuing with the once a day.

Eiry W. Roberts: Obviously, dependent on the data package we're able to generate, we don't currently have a black box currently for suicidality in the TD environment, and we're hopeful that that will continue and that would potentially be an additional differentiator. We'll take our next question from Mark Goodman with SBB. Go ahead. Yes, sorry about the technical difficulties before.

The treatment paradigm, and obviously dependent on the data package, we're able to generate we don't have a black box currently for Suicidality, and and the TD environment and where.

Well I'm hopeful that that would continue and that would potentially be and additional differentiator.

Marc Goodman: Matt, two questions. One, can you just give us a sense of the SG&A line, 2020 versus 2021, just tell us what the increases are, the decreases are, you know, kind of in the business, just so we get a sense of how the money's being spent. And second, can you just repeat your tax rate comment? And when you do exhaust all the NOLs, what is a good tax rate that we should be using as a sustainable one?

Yeah.

And we'll take our next question from Marc Goodman with SVP Leerink. Please go ahead.

Yes, hi, sorry about the technical difficulties before Matt two questions. One can you just give us a sense and the SG&A line 2020 versus 2021, and just tell us what the.

Increases are the decreases are you know kind of and the business. Just so we get a sense of of how the money's being spent and second can you just repeat your tax rate comment and when you do exhaust all of the Nols what is of good tax rate that we should be using as the sustainable. Thanks.

Matthew C. Abernethy: Thanks. Yeah, on the tax front, we're going to start recording a full tax expense here in 2021. What I've said historically is it's around 21% or so. And even though we will be taking a tax expense in 2021, from a federal perspective, we likely won't be a cash taxpayer until 2022 because we still do have $500 million of NOLs entering into 2021.

Yeah on the tax from we're gonna start recording of full tax expense here in 'twenty and 'twenty one what I've said historically is it's around 21 per center. So.

And even though we will be taking a tax expense in 2021 from.

The federal perspective, we'd likely won't be a cash taxpayer until 2022, because we still do have $500 million of Nols entering into a into 'twenty and 'twenty, one and so hopefully hopefully that's helpful. On the SG&A front, what I would what I.

Matthew C. Abernethy: So hopefully, that's helpful. On the SG&A front, what I would say is that you are going to see an increase in SG&A. And it's largely going behind what Eric described earlier, positioning ourselves to be able to grow well with Ingresa and position it both through the pandemic and then as we get out of the pandemic, so a lot going on on the telepsychiatry front as it relates to engaging with patients to have them bring up and ask about their tardive dyskinesia to their physicians. On the R&D side, initiating eight trials this year is going to come with a lot of expense behind it, specific to the Takeda transaction, as well as epilepsy programs. However, we will have a little bit of an offset because of our decision to terminate the Voyager Parkinson's gene therapy program. And that's all reflected in our guidance. So hopefully, that answers your question, Mark. Question from David Omsalom with Piper Sandler: please go ahead. Hey, thanks.

I would say is that you are going to see and increase in SG&A and that's largely going behind what Erik described earlier is positioning ourselves to be able to grow well with the Rosa and the positioning it both through the pandemic and then as we get out of the pandemic that we can have accelerated growth. So a lot going on and the tell us psychiatry front.

And that's going on as it relates to engaging with with with the with patients.

So to have them bring up and ask about their tardive dyskinesia to their of positions on the R&D side of initiating a.

Trials. This year is going to come with a lot of expense behind the specific to the Takeda.

The transaction as well as the epilepsy programs, we will have a little bit of and offset because of her decision to determinate. The the Voyager of Parkinson's gene therapy.

Program, and that's all reflected and and.

And our guidance, but hopefully that answers your question.

Question from David <unk> with Piper Sandler. Please go ahead.

Hey, Thanks, So a question on <unk>.

David Omsalom: So question on, you know, your philosophical thinking on M&A. We've seen some pretty significant M&A of late, certainly quite a large deal in the neurospace yesterday. So I guess with that in mind and what we're seeing with M&A activity, what's your appetite for something that I would term transformational? And to the extent you do have an appetite, you know, where would you take pro forma leverage up to if you were entertaining something like that?

And your philosophical thinking on M&A, we've seen.

Some pretty significant M&A of late and certainly quite a large deal and the neuroscience and.

Yesterday, so I guess with that in mind, and what we're seeing with the M&A activity whats your appetite for something.

And that I would term.

Transformational and to the extent you do have an appetite.

Where would you take.

The pro forma leverage up to if you were entertaining something like that thanks.

Yeah. Thanks for the question you know throw out business development, whether it's licensing or whether it's acquisitions or or whatever the structure of the licensing would be what guides us first is that the science is very strong.

Kevin C. Gorman: Thanks. Yeah, thanks for the question. You know, throughout business development, whether it's licensing, or whether it's acquisitions, or, or whatever the structure of a licensing deal would be, what guides us first is that the science is very strong and it's innovative. Number two, that it is truly addressing the needs of the patients. There, we're not looking for incremental benefits; we're looking for life-changing benefits in everything. So we look at all; that's the lens that we look at in everything.

And it's innovative.

Number two that it is truly addressing the needs of the patients.

There were not looking for any incremental benefit we're looking for a life changing benefits and and everything so we look at all.

Yeah.

That's the lens that we look at and everything and then when we find those things.

Kevin C. Gorman: And then when we find those things, then it just becomes, can the two parties agree on the value of the assets? And past that, you know, if we agree on the value, then actually, we really will do any kind of structure that makes sense to both parties; we're not wed to any one structure. And I think you've, you've seen that.

And then it just becomes kind of the two parties agree on the value of our of the assets and pass that.

You know if we agree on the value then then actually we really well.

We'll do any kind of structure that make sense to both parties. Then we're not wed to any one structure and I think you've seen that.

And the deals that Kyle has done.

Kevin C. Gorman: In the deals that Kyle has done with throughout the last probably three years, that you've, Kyle, do you have anything to add to that? Maybe just to touch a little bit on what Matt said, I think that, first and foremost, we appreciate that programs and assets are scarce. We have a number of high-quality programs and assets in the pipeline currently, and it's our goal to make sure we maximize what we have and execute on the plans that allow us to be successful there. I think that's, that's one message I would send.

With throughout the the last probably three years that you've seen.

Kyle do you have anything to add to that.

Maybe just to touch a little bit on but that said I think debt first and foremost we appreciate the programs and assets are scarce and we have a number of high quality programs and assets and the pipeline currently.

And it's our goal to make sure we maximize what we have and execute on the plans that allow us and be successful. There. So I think that's that's the one message I would say and then the other one would be is if you look back at the pipeline today versus say, one and Grasso was approved in 2017 and the.

Kyle Gano: And the other one would be if you look back at the pipeline today versus the day that GRESA was approved in 2017. In the absence of M&A, but through, you know, probably more traditional business development licensing, we've taken that pipeline from about three programs to about 10 today. And that really speaks to the organization in terms of its ability to look at a number of different programs and bring them on board and start working on the development of those programs. So I think we can show that we've been active and productive in one area, business development. I think when it comes to M&A, then to Kevin's point, we really look at the science and make sure that the programs that we're bringing in really add value to physicians and patients' lives.

The absence of the M&A, but through.

The more traditional business development licensing.

Taken the pipeline from about three programs to about 10 a day.

And I really speaks to the organization and in terms of its ability to look at a number of different programs and bring them on the board and start working on the development. There on those programs. So I think we can show we've shown we've been active and productive.

Two one area of business development I think when it comes to M&A then to Kevin's point, we really look at the science and make sure of the programs that we're bringing in really add value to physicians and patients of lives and they provide the innovation that the payers would be willing to reimburse and help patients get those better.

Kyle Gano: And they provide that innovation that payers would be willing to reimburse and help patients get those medicines. And those types of profiles, if you look at the landscape, aren't readily available in our space, so we look at those very carefully in the context of other licensing types of deals and structures that might allow us to augment our portfolio that way as well.

And those types of profiles.

And if you look at the landscape.

And are readily available and our space. So we look at those very carefully and the context of also the other licensing types of deals and structures that might allow us to augment our portfolio that way as well so opportunistic and tour in terms of of how we approach programs and assets in terms of the structure.

Kevin C. Gorman: So, opportunistic in terms of how we approach programs and assets in terms of structure, but it really goes back to the science. Operator, there are no further questions at this time. I would now like to turn the call back to Kevin Gorman for any closing remarks. Thank you very much.

And it really goes back to the science.

Yeah.

Sure. There are no further questions at this time I would now like to turn the call back to Kevin Gorman for any closing remarks.

You're very much of it and just in closing I'd like to make two comments one is that as you've seen and as you from us.

Kevin C. Gorman: Just in closing, I'd like to make two comments. One is that, as you've seen and as you have seen from us over time, and what you will see from us going forward, we continue to adapt, particularly commercially, to the fluid environment. And I'm confident that we're going to come out, our business will come out even stronger than what we went into this pandemic with. And then also, I'm looking forward to the continued maturation of the pipeline, and as Iris said, several of our compounds are pipelines in and amongst themselves. So, that is a real strength that we have here, and we're going to have a couple of very important data readouts here just this year. So, having said that, I want to thank you all for participating today, and take care. That does conclude today's program. [inaudible] [inaudible] Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers Speakers

Over time, and what you will see from US going forward is that we continue to do adapt particularly commercially.

On the the fluid environment and I'm confident that we're going to come out of our business will come out even stronger.

And then what we went into this pandemic with and then also I'm looking forward to the continued maturation of the pipeline and as I said.

Several of the several of our compounds are pipelines in and amongst themselves. So that is the that is a real strength that we have here and we're going to have a couple of very important data readouts here. Just this year. So having said that I want to thank you all.

For participating today and take care.

This does conclude today's program. Thank you for your participation you may disconnect at any time.

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