Q4 2022 Neurocrine Biosciences Inc Earnings Call
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Speaker 3: Oh.
Speaker 4: Good day everyone and welcome to today's New York and Biosciences Report's fourth quarter and year-end results. At this time, all participants are in a listen-only mode. Later, you'll have the opportunity to ask questions during the question and answer period. You may register to ask a question at any time by pressing star 1 on your touch-tone phone.
Speaker 5: Please note that the call may be recorded and that will be standing by if you need any assistance. It is now my pleasure to turn the call over to Todd Tishla, Vice President of Investor Relations. Please go ahead.
Speaker 6: Thank you and a good Monday morning to everyone. Welcome to Nuremberg's fourth quarter and full year 2022 earnings call. I'm joined by Kevin Gorman, our Chief Executive Officer, Matt Abernathy, our Chief Financial Officer, Irie Roberts, our Chief Medical Officer, Eric Benavich, our Chief Commercial Officer, and Kyle Gano, our Chief Business Development and Strategy Officer.
Speaker 7: During this call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. We'll be jumping into Q&A after prepared remarks, and as is customary, we will do our best to get to all of your questions. With that, I'll turn things over to Kevin.
Speaker 8: Thank you, Todd, and good morning.
Speaker 9: Over the last several years, we have launched a number of initiatives to bring in resident TD patients and lead their suffering. Now many of those initiatives have been very successful as evidence, most recently, by the growth of ingress in 2022, as we announced this morning. We're going to continue to build on those efforts and anticipate continued meaningful growth in 2023.
Speaker 10: TD sufferers are appropriately treated.
Speaker 11: Many of these efforts are aimed at educating healthcare professionals, their staff, payers, and their medical advisors, and importantly, for the first time, patients have groups advocating for the disease and their care.
Speaker 12: Again, these efforts have yielded significant results for sufferers of TD to date, and we will continue that momentum because the vast majority remain undiagnosed and untreated.
Speaker 13: Switching gears, we have a deep and diversified portfolio of mid and late stage medicines that will have important readouts this year and into 2024. We've invested meaningfully in our research and development such that multiple new molecules will enter the clinic each year on a consistent basis to ensure a product flow into the future.
Speaker 14: I'll stop there and without turn it over to Matt.
Speaker 15: Thank you, Kevin. Good morning. Good to see many of you over the past month. With the aggressive sales growth of over three hundred and fifty million dollars in 2022, a record number of TB patients helped and in advancing pipeline, NeuroCarn is in an excellent position for years to come. On the clinical side, CAH enrollment accelerated during the fourth quarter.
Speaker 16: For 2023, we expect another strong growth year for EnGroza with sales of between $1.67 billion to $1.77 billion, reflecting an underdeveloped TD market supported by an expanded sales force and ongoing marketing initiatives.
Speaker 17: For SG&A and R&D expenses, we intend to invest just over $1.4 billion in 2023, reflecting an overall increase in R&D spending primarily related to advancing our 12 mid- to late-stage clinical programs, including our Miska Rennick franchise.
Speaker 18: as well as expanded preclinical research efforts.
Speaker 19: specific to 2023 SG&A expense. While our investment in Egeza will increase to support continued TD growth and the hopeful indication in Huntington, we do expect to show SG&A leverage of around 300 basis points.
Speaker 20: I look forward to your questions later in the poll. Now over to Eric.
Speaker 21: Thanks, Matt. In Gresz's strong performance in 2022 was exemplified by four quarters in a row with year-over-year growth exceeding 30%. Our commercial and medical affairs teams really executed well to help more cardiac dyskinesia patients get treated than ever before.
Speaker 22: and we carry this momentum into 2023.
Speaker 23: carry this momentum into 2023. Yet much work remains ahead of us.
Speaker 24: 7 out of 10 of the approximately 600,000 people in the U.S. living with TD still have not been diagnosed. And half the time, those that receive a diagnosis aren't offered first-line standard of care treatment with a V-MAT2 inhibitor.
Speaker 25: So the opportunity for organic growth for Ingreza remains significant.
Speaker 26: Our 2023 revenue guidance range of $1.67 billion to $1.77 billion assumes approximately 20% year-over-year growth at the midpoint. The low end is a conservative estimate and contemplates precessionary pressure in the U.S., while the high end reflects less macro headwinds and accelerated new patient growth.
Speaker 27: You should anticipate the majority of growth in 2023 to be driven by our psychiatry and neurology business segments, which are the relatively more developed segments of our business.
Speaker 28: Long-term care is a completely new site of care for in Greza, and we are just getting off the ground there.
Speaker 29: Our long-term care team has been making great strides getting up to speed on the unique and complex operational dynamics within LTC and how that impacts TD care.
Speaker 30: While we estimate somewhere in the range of 10 to 15% of TD patients are in an LTC setting, it will likely take a few more quarters before we see a tangible impact to overall sales given the relatively smaller size and higher complexity of that business environment.
Speaker 31: On the patient activation fund, last year's directed consumer campaign exceeded our expected internal metrics.
Speaker 32: So we will continue with that investment in 2023.
Our newest DTC campaign, which we refer to as impressions, is now on the air. The broadcasts, streaming, and digital channels.
The campaign highlights Ingresa as the simple choice with proven efficacy.
And it's the number one prescribed treatment for Cardiopus canesia.
All in all, we're well poised for growth in 2023 and beyond. With that, I will turn the call over now to my colleague, Dr. Irie Roberts, to discuss our clinical progress. Irie?
Thank you, Eric, and good morning to everyone on the call.
2023 promises to be an important year for the neurocran pipeline, with a number of milestones and data readouts, including the August 20th PDUFA date for valbenazine as a potential treatment option for patients with career associated with Huntington's disease.
We were very pleased with the safety and efficacy results from the Connect HD study and with data from the subsequent six-month follow-up, which formed the basis of our supplemental new drug application that was accepted by the FDA in December of 2022.
On the clinical front, I'm pleased to announce that enrollment is complete in both the adult and pediatric registrational studies of cranesophones as a treatment of congenital adrenal hyperplasia.
These trials were designed with input from all key stakeholders, including clinical experts in the field, patients, advocacy groups, and regulatory agencies in the US and Europe .
I'd like to congratulate everyone involved in the Chronosafont program for all their hard work in getting us to where we are today.
This program will provide the largest trial dataset ever generated in patients with CAH, and we look forward to sharing top-line results from both studies in the second half of this year.
In addition to connect the bond, we anticipate reporting studies from two-phase, two-proof-of-concept studies.
NBI 352 for the treatment of focal onset seizure in adults.
and NBI 846 as a treatment for anhedonia associated with major depressive disorder.
Both these top-line datasets are expected in the second half of 2023.
Turning to our growing Mescarinic portfolio, the team continues to make very good progress with enrollment in the Phase II study of NBI 568, a selective M4 agonist for the treatment of schizophrenia.
We also remain on track to initiate the Phase I study of a dual M1 and 4 agonist from this platform, NBI 570 later this year.
To complement this robust pipeline in phase 2 and 3, we plan to continue the growth of our early stage pipeline by advancing additional new chemical entities into phase 1 this year.
I'm very pleased with the current robustness of our clinical pipeline and look forward to further strengthening this pipeline in partnership with our Chief Scientific Officer, Jude Onya.
Under due leadership of research and preclinical development, we're investing in a range of modalities, including small molecule peptides, proteins and gene therapy to deliver on the goal of providing symptomatic.
disease-modifying, and curative treatments for patients living with serious diseases in the field of neuroscience.
As I reflect on where we are as an R&D organization, the foundation and the opportunity for our pipeline has never been stronger.
With that, I'll turn the call back to Kevin. Kevin?
Thank you, Irene. With that, I will open it up for questions.
And at this time, if you would like to ask a question, please press star 1 on your touchtone phone. We'll take our first question from Paul Matisse with Steve-Ole. Please go ahead. Please press star 1 on your touchtone phone.
Hey, thanks so much and congrats on the quarter. I just wanted to ask about the assumptions embedded in your guidance this year. By our back in the envelope math, it seems like the high end of guidance could be met with fewer patient ads and engresms in 2022. Is that accurate? And maybe you could comment on that. And then just a quick aside, what is your guidance?
assume for your expectations for one Q seasonality relative to prior years. Thanks so much.
Yeah, on the new patient front, we do expect to have a very great year here in 2023, over $300 million of year-over-year growth. And I'd say the top end of the guidance range does reflect acceleration in new patients. However, with the bigger base of patients, keeping at a similar attrition rate, we're
You do have a little bit of pressure on what the net new patient ads are. But we overall expect a very strong growth year here in 2023. And as it relates to Q1, Q1 is always Q1.
Patients delay their first fill as they go through the reauthorization process. And we typically have a higher risk than that. Our main mission is to make sure patients stay on medicine. And we've been very successful at that over the past five years. I think that what you see is a little bit slower, Q1.
Thanks for taking my question. This is another question on Ingreza for 4Q. Backing into the growth to net discount based off of the growth metrics that you provided on volume for the quarter. It seems like...
The net price per script was a little bit higher than what you had guided to. I'm getting somewhere in the mid 5600 per script range. Can you verify if that's correct? And also how we should think about the net price in 2023 if we should still expect about 5600 a script. Thanks.
Yeah, net revenue per script in Q4 was in the $5400 range, and you should expect that to be fairly consistent sequentially when you think about Q1. But year over year, as it relates to 2023, you should expect a net price increase of between 3 to 4.
with it Bank of America please go ahead.
Hi guys, good morning. Thanks for taking my questions. Just one from me on, I guess, President Biden declaring that COVID is officially over May 11th. How does that, in any way, affect the way that, I guess, I kind of trust, have been getting paid, you know, with regards to telemedicine?
And then maybe just a quick follow up after that. Thanks.
Hi, Tizin. Good morning. Actually, with the, what we do know already is that the telemedicine mandates that are in from the emergency health order are going to last for two years.
post the emergency health orders um expiration and I think the emergency health order is supposed to expire in May and so you can bet that it's been kicked down the road for about two years post May. So we don't see any changes certainly in 23.
and hopefully we'll know more as we go into 24.
Okay, without that, if it does go back to in office, would that provide you with more certainty on the upside if doctors have to go back into the office?
Our upside did not take into account any changes in the number of physicians back into the office or any changes that have to do with the emergency health order and telemedicine.
Okay, thanks, Kevin.
If you want to take on next question from Brian Scorney with Beard, please go ahead.
Hey, good morning everyone. Thank you for taking the question. I was hoping maybe you could walk through some of your internal assumptions around the market opportunity in CAH given the phase 3 data reading out the latter half of this year. I know a number of years ago you did a commercial day discussing this market when you had an earlier iteration of the program. It does seem like investor expectations around commercial here are somewhat muted.
have crinocerphant in the clinic. It's an investigational medicine, not approved yet for the treatment of CAH, but certainly we're excited about the opportunity that it presents. Just taking a step back, in the US, there's somewhere between 20 and 30,000 people living with COVID-19.
a congenital adrenal hyperplasia, a similar number in Europe as well. Standard of care today is essentially glucocorticoids that are required to essentially replace the missing cortisol for these patients.
What what Kronessa Front is intended to do and what we hope to see in the clinical trial is not only improvement of day-to-day control of the patient's handagents, but also the opportunity to potentially reduce
the dose of the steroids that they're taking for their entire lives.
And so, you know, we certainly see this as a significant game changer in terms of the standard of care.
you know, there are no new treatments for CEH for decades. So really what I built down to is let's see what the data look like. We're excited about the opportunity and there's significant unmet need in terms of being able to help these patients.
improve their day-to-day disease management and overall reduce the potential for long-term issues from treatment with steroids.
Irene, do you have anything to add?
No, I think the only thing I'd add is obviously if you think about the unmet need for patients of CAH, as Eric mentioned, there's been no new treatments that were non-suroidal in nature ever actually in this disease area. And given that our program includes both a pediatric study.
Great, thank you.
And we'll take our next question from Phil Nadeau with Cohen and Company. Please go ahead.
Good morning and thanks for taking our question. It's a follow on to Brian's about the CAH trials. The primary endpoint in the adult trials change in glucocorticoid dose, while the primary and the pediatrics is change in serum A4. Can you remind us why you chose two different endpoints for the two different studies? And then also what the powering of the two trials are and what would be considered clinically meaningful.
dose are very important to patients with CAH and so both of the data sets will be important as we read out the information from both the pediatric and adult trials and so we will be looking at the data holistically across all of the information and we'll be interested as well in clinical outcomes that are embedded as important secondaries into the trial.
the significant variability that you see in pediatric patients associated with some of the physiologic changes that are happening in that patient population anyway, such as growth, development, and other important things. And so, in terms of also then getting to the second part of your question around the powering and steroid reduction and for each of the…
in pediatrics, we're significantly overpowered to see a change in the androgen levels as a primary for that study. And so the number of patients in the trial is more to address safety, tolerability, and also to give us a better insight into the steroid reduction secondary. The same is actually true for the adult study. publishing is here I I do want to note here is called you Hind fullon trial there is a submerge there is an
to placebo. We know from a lot of our discussions with key stakeholders that long-term steroid treatment, particularly at superficial logic levels, is detrimental for patients. And so any reduction in steroid that we see during the program, we believe will be important for patients in the long run.
That's very helpful, thank you.
And we'll take our next question from Chris Shipatonning with Goldman Sachs. Please go ahead.
Thank you. Good morning. For the schizophrenia targeted indications that you have, different mechanisms, complicated disease, can you talk about how you're feeling about the portfolio? If, Ira, you could perhaps share where you think there might be some edge of positioning or probability of success with your pipeline assets.
You're happy to do that, Chris. So, we have three main assets in clinical development right now for the treatment of schizophrenia, and they all actually focus on several different aspects of schizophrenia as a disorder. If you take the furthest along our Phase III program in the same facility, that you would set if you were confused with other daughters who might anomalies between Hassidt's orbit and what type of
for valbenazine as an adjunctive treatment for schizophrenia, we have two studies going on as registration studies addressing that disorder right now. We're very interested in that area because schizophrenia obviously is one of the major disabling neuropsychiatric disorders around the world.
What we've seen from valbenazine in the tardive dyskinesia space is that the combination of antipsychotics and valbenazine is very safe and well tolerated in patients with schizophrenia. And coupling that with some preclinical information that showed synergy of effect in this patient population and also anecdotal data from the field.
The second therapy that we have is Lubodaxistat, which is in phase 2 development. That is a DAAO inhibitor, comes from our Takeda collaboration, and that seeks to address the important cognitive deficit that is seen in patients with schizophrenia, particularly younger patients, given that this is a...
developmental disorder. And so from that perspective, the Luba Daxistat, we had a signal in our phase two study that was intriguing to us in terms of the impact on the backs and scores measures. And so we believe that there is an opportunity there that we want to further progress and further explore in phase two. And so we have a replicate study going on right now. And then the third and
And as you know, this is now a validated mechanism for the treatment of acute psychosis through recent trials that have read out in Phase 2 and Phase 3. So across the board, we think there's a space for all of these different approaches in Phase 3, each address a different aspect of schizophrenia, and given that this is a lifelong disorder for...
and we'll take our next question from Carter Gold with Barclays. Please go ahead.
Good morning, thank you for taking the questions and appreciate all the color on the on the LT care site long term care segment Maybe just to follow up there just give a little bit more detail on some of these operational hurdles and kind of Darkroom's efforts to kind of help the the centers on that front and just sort of what gets you confident That's surmountable in the next couple quarters as you alluded
before we launched back in 2017. So we're excited to be in a position where we've actually put a team in place to really explore that opportunity in LTC. We estimate that 10 to 15% of all TD patients.
are in an LTC setting. And, you know, I mentioned in my commentary that it is a more complex environment. And what I mean by that is that many of these care centers function on a day-to-day basis being run by nursing staff.
And the prescribers, whether it's the medical directors, the consultant psychiatrist or nurse practitioner, they rotate through. So they're not there on a 24 seven basis. They're coming through maybe every other week or every third week. And so,
really what that requires is for our folks to work closely with the staff and these facilities to educate them on Tardive Diskinesia, help them to recognize the abnormal movements, potentially distinguish them from other drug-induced movement disorders.
and importantly identify and flag residents that need further evaluation from the MD or from the nurse practitioner. And so ultimately it takes a team approach in long-term care and you really need to understand that environment.
not only in terms of the dynamics within the facility and who the prescribers are, also the role of the of the LTC pharmacy. And so you know we've been building our understanding of where the opportunity is. We've been narrowing the focus in terms of where we need to spend our time.
And we're seeing good, I think, initial results. And so we're very pleased with the progress that we're making in long-term care. But I do think that in the end, it's still a new space for us and not as far along in terms of level of education and awareness of PDIs, what we're seeing in psychiatry and neurology.
But we're excited about the opportunity and we're going to continue to make progress in 2023. And we'll go next to Miles Minter with William Blair. Please go ahead.
Just back on the catalyst trial, the adult one specifically, just wondering whether these patients are well controlled in terms of their A4 levels on their current glucocorticoid dose. Just curious about that, giving your expectations that you would see additional A4 reductions there.
If those patients are already controlled, how much emphasis we should put on that secondary endpoint. Thanks, Miles. I mean, I think in general patients with CHR not well controlled. I mean, intimately they have some degree of Androgen control, but certainly what we wanted was our trial to reflect.
the real world situation and so it's a requirement in the trial that patients not only have excess steroid dosing but also a lack of control of androgen. So I think there's a real opportunity for us to demonstrate a benefit for patients in the context of these trials both from an androgen control point of view which is the direct action of crinocerfon.
ahead.
Hey, good morning. Thanks for taking my question and congrats on another nice quarter. I have a question on the balance of sales growth versus investment. So you guys are guiding for roughly $300 million in year-over-year growth in Ingreza at the midpoint, but only half of that or less in additional SG&A investment year-over-year. So I guess I'm wondering...
franchise going forward over time. Thanks.
Yes, so I'd say first and foremost we expect a tremendous amount of growth in Ingressa here into the future. Seven out of ten patients still have not been diagnosed to have tardive dyskinesia. So you have to have a growing product to of course drive sgna leverage.
The second piece of investment this year is also preparing for the Huntington's disease launch. So we do have investment associated with that. That is going to be leveraged in particular as you think about 2024 when the growth will more holistically kick in. So don't want to set up an exact algorithm for you in terms of how do you think about it.
We'll take our next question from Jay Olson with Oppenheimer. Please go ahead.
Thank you for the update and congrats on all the progress. Did you talk about the leadership role that Nirocran played in the small biotech exception that was built into the IRA provision for Medicare price negotiations and the implications for ingress as we think about a long-term lifecycle management? Thank you.
Yeah, Jay, thank you. I think Newark can work really effectively with a number of partners, including BIO and other organizations. And so while we think there's a lot more work that needs to be done with the legislation that passes, the fact that the small manufacturer and small biotech exemptions in there are extremely helpful.
Thank you. We'll take our next question from Charles Duncan with Cantor Fitzgerald. Please go ahead.
Yes, good morning. Kevin and team congrats on a great quarter and thanks for taking our questions. I had two brief ones. One is Bell Benazine in Huntington's Korea. I guess I'm wondering if you could remind us as to the not really pricing but the pharmacoeconomic value. Thank you.
of Valbenazine versus Esteto and what is the, call it, target product profile that differentiates it, perhaps even relative to in schizophrenia. My second question is development. That is regarding 846.
I'm wondering if you see that as an adjunctive treatment in depression or a monotherapy.
Thank you.
Thank you. Good morning, Chess. Derek, I'll maybe just take the first part of your question with regards to the value prop for Valvenazine in Huntington's Korea. You know, obviously we're excited about the opportunities there and we're excited about the data that were generated in the HTC.
to promote this into the HD Korea population. And we're well positioned for that, given the fact that we already have extensive footprint in neurology, especially with movement disorder specialists. And so if you think about...
The HD, Korea population only about 20% of patients living with Korea-formed movements are currently getting treated with a B-MAT-2 inhibitor. And, you know, there are reasons for this. Obviously, some folks are turned off or not willing to accept complicated titration regimens.
said is that some of the same differentiating characteristics that we see for valve benzene versus due to trebenazine in a type of dyskinesial, so whole true for Huntington's disease and maybe even more important for them in terms of the simple use, the lack of complex titration.
the lack of food effect and the ability to not have some of the challenges of sitting camp seared in patients with dysphagia. So I think there's several differentiators there that from an important point of view for patients. So we're very encouraged by. With respect to 846 we have a phase 2 proof of concept study in Anadonia and
treatment for their anodonia element. It's a bit early to tell whether this would be an adjunctive treatment or could have the possibility to be used as a treatment as a monotherapy. In the phase two study, we are looking at the anodonia scales in patients on current antidepressant treatment.
But in addition, we will be looking as to whether there's any direct-density to present effect on normal depression scales, the madras as well. And so I think once we read out the data from this study, we'll have a better understanding of the essential path forward.
In addition, we will be looking as to whether there's any direct antidepressant effect on normal depression scales, the madras as well. So I think once we read out the data from this study, we'll have a better understanding of the potential path forward.
Okay, we'll take our next question from Laura Chico with wet bus securities. Please go ahead.
Good morning. Thanks for taking the question. Just a quick one with respect to the diagnosed TD population. So you're estimating approximately 30% of TD patients are now diagnosed. I'm wondering if you could speak to the typical duration of treatment that you're seeing among the diagnosed patients. How long are TD patients remaining?
on a VMET2 inhibitor once they start. And just out of curiosity, how frequently are patients coming back to treatment and just wondering what drivers might be contributing there. Thank you.
And going into this launch, you know, certainly we expected that compliance with Engroza would be similar to other medicines that these patients are taking for their underlying psychiatric illnesses. Sometimes you might want to adopt something that
consistent with what you see, for example, with antidepressants or with antipsychotics. We've actually been very pleased with the persistency that we've seen subsequent to the launch, better than what we expected. So, certainly that's an important driver of growth and has been really since the early days of the launch and has continued.
the actual persistency is with Ingreza. And then with regards to the overall patient population, we estimate it to be around 600,000 in the U.S. There are other estimates that are out there that are larger. However, if you look at the progress that we've made over the last five plus years since the launch.
However, there's still a lot of work to do. Still seven out of 10 roughly, patients living with TD have yet to be given a diagnosis or really any explanation for their abnormal movements. And about half the time when patients are diagnosed, they're not offered treatment with a V-MAT II inhibitor, which is the new standard of care.
So, you know, we see a lot of opportunity for improvement and, frankly, a lot of opportunity for organic growth within Greza in the TD patient population. We feel good about the progress we've made, but we recognize that there's a lot of work ahead of us. Thanks.
lot of opportunity for improvement and frankly a lot of opportunity for organic growth within Gresa in the TD patient population. We feel good about the progress we've made, but we recognize that there's a lot of work ahead of us. Thanks. Thank you.
We will take our next question from Anupam Rama with J.P. Morgan. Please go ahead. We will take our next question from J.P. Morgan.
Hi, thanks for the question. This is actually in Balthankuto, on Drawtop. You had previously mentioned Salesforce pull through, expected around 3Q. What metrics are you seeing or tracking to best understand that? Thank you.
Yeah, what we look at, you know, is both.
leading and lagging indicators. And in our expansion of 2022, we hired experienced sales people in neuroscience, both in psychiatry and in neurology. And so they come in with a lot of experience and relationships.
What they don't have is the direct experience in the TD market. And so that takes a little bit of time to learn. This kind of sales job, I think, is different than maybe selling an antidepressant or an antipsychotic, for example, in the sense that there's a lot of disease education that occurs really across all these care settings.
And we help our customers recognize TD. We educate them on the diagnostic criteria. We use a lot of videos to help them recognize different presentations of TD across different patient types. And not only do they have to help our customers with the diagnostic process.
And so what we've seen in the past when we've expanded our team is that it took a few quarters for the new salespeople to get up to the same level of proficiency as the legacy team. And we saw that this time around as well. Certainly we believe that the expansion of our field organization.
contributed to the strong growth that we saw in 2022. However, you know, we do believe that they're still upside from that expansion that we're going to see going forward. Thank you.
We'll take our next question from Mark Goodman with SVB Securities. Please go ahead. Yes, good morning. Irie, can you talk about the epilepsy data that's coming in the second half of the year and how you look at this product as a potential differentiator in the epilepsy market? And then Matt, can you maybe help us just a little with…
Expenses, just maybe anything unusual, how they'll be spread throughout the year and just update us on tax rate and how you're thinking about that this year and the next couple of years. Thank you so much!
Okay, thanks, Mark. So, the epilepsy study that we have ongoing right now in Phase 2 for our molecule 352, which is a selective NAV 1.6 channel antagonist, it's a focal-onset seizure study. Focal-onset seizures are the most common seizures seen across the...
shows a lack of control from their current treatment. The endpoints for the study is the 100 patients. The endpoint is a change from baseline in the seizure frequency measured over a month's baseline period and then compared to the last month of treatment. And the overall treatment period is up to 13 weeks.
In terms of the differentiation, if we think about the 352 as a selective NAV 1.6 antagonist, the majority of currently available anti-apoletic therapies have broad pharmacology and associated with the somewhat unsavorable benefit risk profiles. So the...
solubility and side effects that are seen with currently available treatments. Obviously this is a phase two study we're on track to read out the data in the second half of this year and based on what we see there we'll be considering next steps if we're successful. So real quick on the spending front the only item that I would call out from a timing or seasonality perspective is we've historically seen
during the first quarter. From a tax perspective this year, I'm expecting an effective tax rate of between 24 and 25% on the cash tax side. We burned through all of our NOLs in 2022 as a result of the tax legislation associated with capitalized R&D.
And so as a result of that, we will be a federal cash taxpayer here in 2023. Still holding out some level of hope that that might be put on hold in terms of the cap wise R&D tax.
legislation, but for now, what I would guide you to is that we would be expecting to be a full federal cash taxpayer this year.
Thanks.
Once I got an expression from Ash Verma with EBS, please go ahead.
Hi, thanks for taking my question. Congrats on the quarter. So for the 568 muscarinic phase 2 trial that you have, you previously said that it's a dose finding study. Can you share if it's a once daily or twice daily molecule? And from your perspective, how much would the dosing frequency matter for comparison?
in patients with acute schizophrenia, acute psychosis. The enrollment in that program is going extremely well right now, and we're looking forward very much to seeing both the impact of this M4 selective agonist on the symptoms of psychosis and also, obviously importantly, this safety and tolerability profile.
Thanks. And we'll take our next question from David Amselin with Piper Sandler. Please go ahead. Thanks. So on the most erratic portfolio, you're building the Selective M4 568 is...
offering the potential for an improved safety profile. So I guess with that in mind, I'm wondering if you could better articulate how you're thinking of the value proposition of the dual M1, M4 and what kind of role that would play as you think about pipeline and from a competitive perspective. And then secondly, as you think...
the portfolio here. What's your view on the potential beyond schizophrenia particularly in for the muscarinics and mood disorders say bipolar mania and how are you thinking about development there? Thank you.
Wow, there's a lot of questions in there. Thank you. So we are very excited about the portfolio of assets that came to us from the collaboration with Sose Hepatitis and I think that's one of the real strengths of this collaboration in our mind. I mean clearly the M4 agonism is a validated mechanism.
in the treatment of acute psychosis. I think that's been confirmed both in phase 3 and phase 2 clinical trials now. But through mechanisms different from direct for direct agonism, you have obviously the pan agonist of the normal entropium combination, and then you also have the cerebellum. So with anSeg polarizing enzyme,
positive allosteric modulator which requires the presence of acetylcholine to be effective. And so in the context of the M4 selective agonist, it's really early to be able to make a statement about differentiation around safety. Our trial in phase two is designed to give us an initial estimate of...
dual agonists. Beyond schizophrenia, we believe there is a significant degree of opportunity for this platform in diseases impacting cognition all the way through from Alzheimer's to neuropsychiatric disorders that are impacted with deficits in cognition. And in addition, I think your commentary around bipolar also makes sense in terms of
Sosaheb Taurus, positions us uniquely out there in the muscarinic world in that we can test the hypotheses within man with a number of specific compounds. An M4 specific agonist, an M1, M4, and an M1. And so we'll be able to tease out and elucidate exactly the pathways.
put the takes of tardive dyskinesia in the long term care setting. Now this could be a significant driver on just given population dynamics. I guess kind of Warren, what is the plan for reaching these patients to providers or patients assuming that DCC is probably not in the question here or out of the question here. Thank you. Thanks.
that are essentially run by nursing staff 24-7 with providers that rotate through, whether it's the medical directors, the consultant psychiatrist, the nurse practitioner, the consultant pharmacist. And our team really has worked to understand what are the dynamics locally.
in terms of these facilities, who are the facilities that the providers are rotating through, what's their relationship with the LTC pharmacies, and this kind of building what I would call an outside-in account management approach, so that you can work with a number of providers, but really affect the much more than the people that are in the facility.
flag those residents, bring them to the attention of the providers so they can do a full differential diagnosis. And so it's a team approach. It's a more complicated environment than what you see in most outpatient clinics.
And in some ways it's more similar to what you might see, for example, in a hospital environment in terms of how you need to sort of manage those accounts. So, you know, we're excited about the opportunity. We are seeing good progress there. It's not nearly as developed, as I mentioned earlier, as the psychiatry and neurology business.
So we feel good about the progress we're making and you'll hear more about that as we move through the year.
progress we're making and you'll hear more about that as we move through the year. Great, thanks.
And we'll take our next question from Ami Fadia with Needham. Please go ahead.
Hi, good morning. Thanks for taking my question. Can you talk a little bit about the Huntington's disease career with the awareness that physicians have within Grazer and TD? How do we think about the ramp of the launch and that indication?
If you could talk about that in CH, perfectly. Can you talk about where the patients are treated and if there are differences in how and where patients are treated in Europe as opposed to the US?
I'll take the second one first, Ami. Thank you for that. I think it's pretty consistent in how patients with CAHR are treated. It's usually in our experience in expert endocrinology clinics. These clinicians know their patients well. We certainly don't have an issue of diagnosis here. I think we have seen a lot of similarity as we've run these global trials.
Yeah, with regards to the first part of your question about the dynamics within the Huntington's community, I'll start off by saying that we're excited about the data that we've generated and certainly look forward to getting the labeling from the FDA later this year.
We have complete coverage of the movement disorder neurology community with our existing neurology sales force. And obviously, we need to introduce the data and the label to those neurologists that are treating these Huntington's patients.
but this doesn't require any kind of significant lift or change to our commercial footprint. So this is really another opportunity to create leverage with our existing infrastructure and we're excited to bring what we think will be a differentiated product to a population in need.
And we'll take our next question from Yachtine Sune with Guggenheimer Partners. Please go ahead. Hey guys, thank you for taking my question. Two part question. First is, I mean, you have three major capitalists this year. You have the focal on.
probability of success especially on the focal onset and CH where you know there is sort of more mechanistic rationale and then if you can also talk about the anodyne why do you think the GPR when 3-9 agonist might be more sensitive
in these patients and what should we anticipate on the end point that you are evaluating the DARS end point that you are looking at in phase 2. Thank you. Yeah, Jatin, you asked a few dozen questions in there. We could probably spend the better part of the hour of this call in going through that.
What I'm looking forward to is as the year goes on to be able to talk about each of these programs in greater depth and as we get closer to data, obviously we're going to be speaking about them. So I'd like to basically put your questions on hold until we have a better forum where we can …
to hit each one of them in detail. All right, we'll take our next question from Sumant Gookani with Canaccord, please go ahead.
Good morning. Thanks for taking my question, which is in effect an expense management one. Given the timing of your recent new gene therapy collaboration with Voyager, are you thinking about your stake in Voyager as a longer-term strategic one, or does the timing of your transaction allow for some tactical moves that could allow you to defray some SGNI expense related to the R&D expense related to GBA1 associated?
program in the near to mid-term, especially if Novartis opts into its collaboration with Voyager in the current quarter.
Yeah, so from an expense management perspective, this wasn't done for any type of expense management. There will be not a ton of burn right here in 2023, but it really puts us in a position to have an expansive gene therapy preclinical portfolio that's going to put us in a position to be able to hope.
flexibility here even post the upfront payment that we'll be making. And so it allows us strategically to continue to make larger or different investments even outside of gene therapy as we look forward. Thank you. Thanks. All right. We'll take our final question. So a great way to do this is you try to overcome memePlanet,entscape? Yes fashion.
are going to be a little bit of challenge. To that end, how do you foresee potential challenges there, given that glucocorticosteroids are cheap? What can you do to help payers understand the profile of the drug? And is there a bar in terms of clinical efficacy that would basically move them over? Thank you.
are going to be a little bit of challenge to that. And how do you foresee potential challenges there, given that you go quite a quick story, I'd say cheap? What can you do to help people understand the profile of the drug? And is there a bar in terms of clinical efficacy that would basically move them over?
Yeah, so I'll just comment quickly on the pair front. You know, this is a disease area where we're going to have to educate pairs, similar to what we did with Tardive dyskinesia. The thing that it will be emphasizing with pairs is that the de-patients are often very poorly managed.
The steroids are an important treatment that keep them alive, but most patients are either at any given point in time either over treated or under treated with their steroids. And therefore, their disease is not well controlled. And that's really where the value story for Kronasarphan comes in to improve that disease.
the provider and patient communities, but also to work carefully with the payers so that they understand the value proposition of Cardenasur font and where it fits in in terms of the overall treatment landscape.
Super helpful. I want to thank you all. I want to thank you all for your questions in my. I have just a couple of final remarks here. First and foremost, we're looking forward to a very strong 2023, which is evidenced by the guidance that we gave you for ingressa and looking forward to.
and the goal of the company is to become the leading neuroscience company in the world. And we broadly talk about neurosciences being neuroindocrinology, neurology, and neuropsychiatry. It's interesting if you look at the three data readouts that we have this year, C-A-H-F-O-S, and Adonia.
They cover all three of those areas of neuroscience. And with that, again, I'd like to thank you for all the questions you had and look forward to getting together with you in the coming months. Take care. Thank you, and this does conclude today's program. Thank you for your participation. And you may disconnect at any time.
all three of those areas of neuroscience. And with that again I'd like to thank you for all the questions you had and look forward to getting together with you in the coming months. Take care. Thank you and this does conclude today's program. Thank you for your participation. You may disconnect at any time.
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