Q4 2022 Ultragenyx Pharmaceutical Inc Earnings Call
Yeah.
Good afternoon, and welcome to the Altra genetics fourth quarter and full year 2022 financial results Conference call. At this time all participants are in a listen only mode. At the end of the prepared remarks, you will have the opportunity to ask questions. During the Q&A portion of the call. It is now my pleasure to turn.
The call over to Joshua He got executive director and head of Investor Relations.
Thank you.
Issued a press release detailing our financial results, which you can find on our website at ultra <unk> Dot Com joining me on this call our ammo caucus, Chief Executive Officer, and President, Eric Hare, Chief Commercial Officer, Camille Bedrosian, Chief Medical Officer, Eric Olson Senior Vice President of corporate strategy and finance.
And Pat I think our chief accounting 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. Please refer to the risk factors discussed in our latest SEC filings I will now turn the call over to him.
Thanks, Josh and good afternoon, everyone.
Some of you may have listened in on my presentation at the recent Jpmorgan Health care conference, where I talked about our focus for areas for 2023.
Over the last year, we completed several strategic investments aligned our teams and resources around the highest value generating program for the company.
This year, we will continue to focus on operational efficiency, while generating data from our key clinical programs and the Angelman osteogenesis imperfecta in our pivotal gene therapy studies.
In 2022, we generate more than $350 million of global revenue in our fifth year as a commercial company.
Here, we expect revenue to be in the $420 million to $450 million range from our four products across five indications.
We expect a steady revenue growth to continue as existing products are still in relatively early phases of commercialization.
At the same time the investments made over the last few years have positioned us to drive meaningful value from large opportunity programs like Gtx, one two for Angelman and UX, one port III brought Genesis imperfecta.
And we have more recently bolster our business with additional strategic steps.
Specifically, we secured a license and collaboration agreement to commercialize that Keith a preclinical homozygous familial hypercholesterolemia in countries outside of the U S, which will leverage our global commercial infrastructure and capabilities.
We acquired global rights UX 111 in AAV gene therapy for the treatment of Sanfilippo syndrome.
M Abbey O&M based on the strength of the pivotal marker data and clinical data generated in the transfer a study.
We all think sized our option to acquire <unk> TX following.
Interim data from the phase one two of Gtx 102 for.
For the treatment of Angelman syndrome.
The <unk> acquisition gives us full control over that program.
And we completed the build out of our gene therapy manufacturing plant in Bedford, Massachusetts, which is expected to begin production. This spring this.
Facility and our manufacturing capabilities grants us the ability to better control the timing cost and scale. The production of our gene therapies, establishing us as a commercial ready gene therapy company.
Within our pipeline, we made strong progress over the past year. In addition to progressing arrangement program.
The initial initiated a pivotal phase III program for <unk> for three and Oh I'd have completed enrollment of the phase II portion of the study with.
We advanced <unk>, one 401 into pivotal phase III study for GSD <unk> enrolled the last patient into the baseline screening period.
We also initiated a phase III study of <unk>, 301, and OTC, where we have randomized and dosed. The first patient in this study with additional patients and the baseline screening period.
And we initiated and dose patients in the pivotal seamless study of <unk> 701 for Wilson disease.
As a commercial company with growing revenue in a diverse late stage clinical pipeline, we recently a valid ways to improve our operating efficiencies.
We will focus on leveraging our established global infrastructure actively managing expenses and head count to drive value from the commercial launches and execute on our most important clinical programs.
With that I'll turn the call over to Eric to provide more specifics on the commercial programs and their successes last year.
Thank you Emil and good afternoon, everyone.
1022 was an important year for the commercial and field teams across all the products they delivered 35% year over year growth overcoming some of the early challenges.
Rented by the <unk> variant.
Revenue from <unk> in our territories grew 34%.
<unk> grew 41% MF savi, our ultra rare product grew 29%.
Team's efforts.
Our proven rare disease products can generate meaningful revenue growth five plus years after launch.
2022 was also the first year, where global sales of Christina exceeded $1 billion.
Crossing that threshold was made possible through the ultra genex team's efforts that led to approximately $700 million in total product sales across North America, and Latin America and also the efforts of key our caring in Europe and Asia.
Since launching <unk> in April 2018, we have established a strong base of business that we expect will continue to grow as we transition the primary commercialization responsibilities to Kiara Karen in April of this year.
In the U S. We added approximately 110 start forms in the fourth quarter and approximately 90 patients on reimbursed therapy, along with 50, new unique prescribers. These.
These metrics are nearing their pre pandemic levels and support the 26% annual revenue growth.
In this region.
This is particularly impressive as the team has shifted efforts defining adults into harder to reach community clinics, where more than 50% of our star forms of generation.
Which combined key our Kieran and ultra Genex field teams in Q4, we have started to reach many more prescribers in the community and raising awareness of XL H, which has helped us in our patient finding efforts.
In Latin America, Chris Vida continues to grow supported by additional regulatory and reimbursement approvals and also from from steady demand in the pediatric and adult setting.
We ended 2022 with approximately 300 patients on reimbursed therapy in this region and we expect this will continue to grow as more and more prescribers and see the benefits their patients experience from Christina.
As this is it.
It's common in this region.
Ordering patterns drive some quarter to quarter variability in revenue.
But the underlying demand continues to grow at a steady pace.
In 2023.
We updated the regions for which we will issue Chris feet of guidance.
This does a better job of representing the broad reach of Christina and the total revenue two ultra genetics at.
At the beginning of the year and reaffirm today, we issued guidance of 325 million to $340 million for Christina in North America, Latin America and Europe .
This is inclusive of all types of revenue by their profit share.
Royalty cash or noncash.
Compared to 2022 for the same regions and types of revenue. This range represents between 16 and 22% growth.
Turning now to the job where I'll begin with the team's work in the U S.
In 2022, we were encouraged by truly strong patient demand.
Ended the year with approximately 425 completed start forms with approximately 375 patients on reimbursed therapy.
The number of unique prescribers prescribers continues to grow now with approximately 190 healthcare providers, writing at least one prescription for the jewelry.
In 2023.
We will be focused on continuing to educate healthcare providers on the benefits of the dose titration supported by our clinical studies to ensure patients are able to achieve optimal dose titration.
In Europe demand for <unk> continues to be led by the named patient and early access programs, particularly in France and Italy.
We have also begun to see requests come in from Germany, Austria, and certain middle East countries.
In Latin America.
We are continuing to work through the process leveraging our <unk>.
Our existing infrastructure to expand across the region and.
In Brazil <unk> is currently approved and we are working through the process to get full reimbursement approval from the Ministry of finance.
We also anticipate additional country regulatory filings in the region later this year.
Across all regions, we expect 2023, <unk> revenue to be between 65 and $75 million.
We are reaffirming the range, we announced last month.
This represents between 17% and 35% growth over 2022.
At the beginning of the year, we also issued guidance for total revenue.
Which we are reaffirming today.
The range of $425 million to $450 million represents 20 plus percent growth versus 2020 to.
It includes estimates for <unk> and <unk> that I, just mentioned and also includes mesh savvy and ftes.
With that I'll turn the call to Eric to share more details on the financial results for the quarter.
Thanks, Eric.
Earlier today, we issued a press release that included financial results for the quarter, which I will briefly summarize.
Company revenue for the 12 months ended December 31, 2022 totaled $363 million.
<unk> revenue estrogenic territories with $258 million, including $215 million from the North American profit share territory, and net product sales of $43 million in other regions.
Total royalty revenue related to the sale of that Chris Vida in the European territory was $22 million.
The jewelry revenue for 2022 was $56 million.
<unk> revenue for the same time period of $21 million.
Our total operating expenses for the year ended December 31, 2022 over 1 billion, which included R&D expenses at $706 million SG&A expense of $278 million and cost of sales of $28 million.
Operating expenses for the year include noncash stock based compensation expense of $130 million and a one time R&D expense of approximately $75 million related to our acquisition of Gtx.
For the year ended December 31, 2022, net loss was $707 million or $10 12 per share.
We ended the year with approximately $900 million in cash cash equivalents and marketable securities.
In 2023, our net uses of cash are expected to decrease significantly as we leverage our established infrastructure and continue to grow the top line.
This will be enabled by financial discipline revenue growth and operational focus on our late stage clinical portfolio.
While we have improvements in net cash used will be partially offset by the portion of our crews. We had in North America royalty that will now go to our financing partner, we are confident that the continuing strength of our business fundamentals will allow us to drive towards profitability in the coming years.
Now I'll turn the call back to able to briefly recap the 2020 free clinical catalysts.
Thank you Erinn I'll summarize the catalyst from our broad and diverse clinical portfolio before we open up for Q&A.
Starting with <unk> III for us to use Jeff's imperfecta, the truth <unk> Anti school Roston mechanism provides the unique dual action to address the body's maladaptive response to the bad collagen.
<unk> unique Maxim stimulates more osteoblasts to mature into bone, making cells and make those cells increase their bone production, while also limiting bone resorption.
The phase II portion of the studies are fully enrolled and we expect to share these data and transition to the phase III in mid 2023.
Separately, we are playing initiate a young pediatric study that compares to the truth of the mab to Bisphosphonates to assess total fractures in a younger patient population, which have a much higher fracture frequency.
Next Gtx 102 in Angelman syndrome.
We are continuing to see encouraging signs of clinical activity across the patients who had been dosed under the amended and expanded access protocols.
We recently began screening patients in both expansion cohorts and expect to provide the next data update based on a larger number of patients in the program later this year.
Turning to the gene therapy programs with USD 111 for Sanfilippo syndrome, we're expecting to have a meeting with FDA in the first half of 2023 to discuss the plan to file for accelerated approval based on a biomarker endpoint.
For <unk> hundred one for GSD <unk>, we enrolled the last patient in the baseline screening period for the pivotal study earlier. This year once the patient has been dosed a 48 week clock will begin we expect to share the phase III data in the first half of 2024.
<unk> hundred one for OTC deficiency dose the first patient in the phase III study earlier this year.
We anticipate enrollment of this study will increase momentum as more patients make it through the baseline screening period.
<unk> several one for Wilson disease enrolling patients in the dose finding stage, we expect us to be complete in mid 2023 with a data on safety and initial signs of clinical activity expected in early 2024.
Finally, <unk> III, our mrna program for GSD three.
Will has completed enrollment in the single ascending dose cohorts of the phase one two study and we expect to have these data in the first half of 2023.
Based on these analyses and other work will then review our plans for the next steps in the program.
I founded <unk> in 2010 13 years later, we have four commercial products and are approaching revenue $450 million. We also have one of the most robust late stage clinical pipelines and rare diseases. We're now poised for the next phase of the company with growing revenues fueling our development of new pipeline priority.
In the coming years, a growing revenue base financial discipline.
And larger indication opportunities will allow us to reach profitability, while also leading the future of rare disease medicine.
With that let's move on to your questions. Operator, please provide the Q&A instructions.
Good day, ladies and gentlemen, if you have a question at this time. Please press star one one on your telephone. If your question has been answered and you'd like to remove yourself from the queue simply press star one again to remove yourself from the queue. We ask that you. Please limit yourself to one question and one follow up you may get back into the queue as time allows our first question.
Comes from the line of Gena Wang from Barclays. Your question. Please.
Thank you for taking my questions. So I will ask one question each for Angelman program and also osteogenesis imperfecta four and your lung program. What are the doses you selected for the expansion cohort.
And then for the osteogenesis imperfecta.
Thank you update how would you use first can you remind us the two doses used in the orbit phase two portion and how would you use.
Biomarker response <unk> of bone mineral density to establish dose algorithm.
Phase III portion.
Great. Thank you gena, so and the Angelman, we've been of course evaluating higher doses and through a dose titration period, we haven't put out what doses. We are using but we've established some doses that we believe have an appropriate benefit risk that will be using the expansion in both loading patients.
And in their maintenance levels, we've put some information out of the range of doses that we have been trying but we'll put out more information when we have it on the exact doses we are using.
With regard to ask Jeff's imperfect.
We're comparing two doses in both children from ages five to adults 25, and we're comparing 'twenty to 40, our expectation is that the younger children may need more drug in order to get enough concentration of antibody using pharmacokinetic analysis.
To achieve the optimal result, so we'll look at the concentrations of drug in the young and the old.
And we'll also look at the Biomarkers for bone production <unk> NP.
And we will have also some bone mineral density data as well and the goal is to compare those and determine do we need to use a higher concentration of drug in the younger patients to achieve the optimal effect or not so look at this as dose dose tuning rather and dose finding we know the dose. The question is do we need to go a little higher in the younger patients.
Youll get a little read on what this drug does in young patients at that time, which I think will be more responsive patients than the older patients had been treated before that's at least our expectation based on bone disease, we've created in the past.
Thank you. Thanks, operator next question.
Certainly once again, if you have a question at this time. Please press Star then one one moment for our next question.
And our next question comes from the line of Chris Ramsay from Piper Sandler Your question. Please.
Hey, Thanks, just one question on a collaboration that I don't think I've heard you guys talk about.
So enzyme today mentioned that they've just started a collaboration with you guys defined misdiagnosis E&P one patients.
It seems XL H seems to overlap maybe seen it typically with that disease.
This asset would seem to be something that would I would think fitting within your wheelhouse developmentally just kind of curious if you had any thoughts on this collaboration and maybe.
Any thoughts on the drug itself.
Especially in light of the data that these guys had <unk>.
These topline today and how youre thinking about this relationship going forward.
Yeah, well, we work with a lot of companies on the issue of diagnosis and not just in design. Other companies. We're all trying to help find patients and share that information with each other.
At this point, we're not planning on bringing any more products into our portfolio and we continue to watch the field, including what Amazon is doing and others with regard to new opportunities for rare disease, but at this point we have we.
We have on our play at all we need to manage and but finding patients and working with our partners.
And others in the field is something we do routinely.
Great. Thank you.
Yes.
Thank you one moment for our next question.
And our next question comes from line of Joon Lee from <unk>. Your question. Please.
Hi, Thanks for taking our questions.
I think we await the biomarker data for us it's just math.
Is there a level of one formation you wouldn't want to exceed our there close with safety issues, particularly in young patients, but growing bone, where too much bone formation could lead to potential safety issues maybe.
Hearing loss for example, thank.
Thank you.
Yes. Thank you. So the question is whether you can give me like too much.
Bone growth kind of impinged nerves like.
In hearing or otherwise.
The truth is these patients are very deficient in they're bound production. So we're starting from a place of deficiency and while if you had a generic defect score Austin you might get these problems the ability for us to knock down the level of cross to the degree required I think is very different from a genetic deficiency state.
Secondly, I would say where the patient are beginning at a position of very deficient phone quantity as we treat them and grow we will look at after we've improved their bone strength at a point of establishing a maintenance dosing and based on the the asteroid study where we.
<unk> was stopped and we've looked at resort option.
Looks like we can establish a let's say less frequent maintenance dosing once we get patients fully loaded and having their bone strength improved which I think would mitigate it for example, if there was a long term risk of that kind, but let's face. It right. Now. These patients are suffering every day their bones are disintegrating and that's first order of business, but we will always watch out for.
Sure.
Managing the effect of our drugs going forward, but at this point, we're not concerned about it in the beginning of this program.
Next question. Thank you one moment for our next question.
And our next question comes from the line of equal <unk> from Citi. Your question. Please.
Hi, and thank you for taking my question. So obviously, we are getting a lot of questions lately on the Oi program and Romo. It comes up quite a lot in that conversation, which obviously as you know is an emphasis for us and so if you could help us with the quick elevator pitch on why <unk> is differentiated from Romo and why Youre antibody will be the preferred option.
Potentially in NOI.
<unk>.
Sure first of all I'm Roma was designed and developed for treatment of osteoporosis and approved and labeled in that area.
Where we're going to be doing is dose optimizing for the us jets imperfect indication not the Austin growth indication. They have a limit of 12 months of treatment and we will not have that limit we will be able to have chronic dosing, which will be very important in this disease, which is lifelong.
And secondly by optimizing the dosing regimen will be able to treat.
Treat patients in an optimal way is a rare disease company well to be able to support patients specifically so the combination of the dose regimen and support programs will will differentiate us to choose the mab from what I'll refer out there Romo right now.
So those are some of the factors I think that will be important.
Okay. Thanks, and just a follow up on Gina's earlier question regarding the dose selection for the <unk> study that youre going to readout in the middle of the year. Once you select that dose will that be the same dose that is used in the younger patients in the two to five year olds, when youre comparing head to head versus Bisphosphonates.
Well if that dose for example turns out to be higher if 20 isn't the dose needs to be higher will then adapt that over to the other study dose as well.
We would expect to.
Okay got it thank you.
Thank you one moment for our next question.
And our next question comes from the line of <unk> Ahmad from Bank of America. Your question. Please.
Hi, good afternoon, thanks for taking my questions.
I just wanted to follow up maybe on the opportunity in sanfilippo syndrome.
111 can you just remind us what the competitive landscape looks like today and how many patients do you think there are in the U S and abroad and then a quick follow up on your manufacturing facility on the new one would that support all of your gene therapy program going forward.
Thanks, <unk>, so with sanfilippo 381 of the decisions we had to make in picking up the program with whether there was a very good option around that we could do just as well in our view was there wasn't really the other programming life team there actually.
They are going out of business.
This product was better than that product I think from a standpoint of biomarker reductions in effect.
There is a.
A lentivirus approach, which I think is has its own challenges it's fairly early on but really there isn't another I think effective.
Gene therapy out there that set the stage so our feeling was that this would be.
The lead program and had the best efficacy that I've seen from at least the biomarker standpoint.
So that was our decision with regard to the population of the world.
Theres, probably a few thousand patients but.
You have to think of this as a little bit more of an incident population right because.
The best effect appears to be in kids Theyre under two years old so it's a little bit like <unk>, they need to be young to get the best benefit would we treat older patients perhaps it depends on what happens in the regulatory process I think there may be benefit in older patients, but it's clear the optimal benefit happens when you treat young so I would look.
At it that way.
I would say to you about this gene therapy and unlike some of the other diseases, where there are other treatments. If we add a gene therapy. That's doing what we believe we see it's doing right. Now we think essentially every sample a patient would want to get treated because the other options are just none at this point in time and so.
It has the kind of devastating impact that you have with SMA and I think the adoption rate would be very high if we can get it approved promptly.
Now the other question was the manufacturing plant and capacity.
The plant is two three to can run 30 runs a year. One suite is operating right now we will we.
We can operate a second suite 30 runs years get a lot of what we need done.
I don't know that we'll handle 100% of the needs because it depends on which programs you are talking about to achieve that our plan has always been to have some hybrid some contract manufacturing and some of our own and if necessary. We do have a green space a greenfield plant space next to our plant that we could double the plant further.
But right now I think 30 runs will take us a long way in the future and if we're at that high level success rate trading that many gene therapies. We can then invest in expanding that capacity further but it will take us a long way with for what we need at the moment.
Thank you one moment for our next question.
And our next question comes from the line of Jeff Hung from Morgan Stanley . Your question. Please.
Thanks for taking my questions I guess first features and App you've talked about the two doses what kind of incremental benefit would you expect or want to see with the 40 milligram per kilogram dose over the 20.
And then can you talk about the feedback that you've been hearing on the launch of <unk> in Europe .
Yes.
So, let's say <unk> mab.
We haven't set precise criteria, we really want to look at the gradations of drug concentration drug effect as we go along.
To give you a rough idea of if there were if doubling the dose gave you 10% more foam production I don't think it's worth it but if I gave you a 50% more bound production then I would say that's worth it. So if that gives you a kind of a rough idea.
I think that would be what we would be looking for is something more meaningful to warrant spending I'm, giving that much more drug.
With regard to have Keith.
We've had tremendously positive feedback from doctors on it both in Europe , and we've had a few compassionate use requests in patients treated and.
I think that we're excited about potential at <unk> is really the first really good drug that doesn't depend on LDL receptor at all.
And can be given just as a once daily IV and.
So if we can get it reimbursed and get it get access out there I think we will see.
<unk> uptake because there is great interest in it and as part of the reason, we we decide to.
Partner with Regeneron on the program in the first place.
Thank you one moment for our next question.
And our next question comes from the line of Salve in Ritchie from Goldman Sachs. Your question. Please.
Alright. Thanks, so much for taking a question. This is tommy on for solving so further UX 53 data coming this year can you remind us what some of the details here arms, Dan in terms of duration number of patients in any virus or benchmarks, where you would see a positive signal. Thank you.
Certainly the <unk> three program is an mrna LNP that's producing.
This enzyme that will.
To help restore glycogen metabolism.
We will be looking for changes in biomarkers and glucose release in biomarkers of glucose.
Fragments that are accumulating.
As well as safety parameters around.
Liver immune response et cetera, so it will be primarily a biochemical kind of look at both glucose control as well as <unk>.
Release of glycogen fragment. So those two things should help us get an idea about dose. These are all single dose patients that were escalated.
It's single dose ascending dose cohort so.
It'll be a first indication of what we can achieve in terms of metabolic correction based on primarily biochemical measures.
Thank you one moment for our next question.
And our next question comes from the line of Maury Raycroft from Jefferies. Your question. Please.
Hi, Thanks for taking my questions I was wondering for the sutures My page to update can you clarify if youll have all patients at each of the two doses and the age range is 5% to 25, but are you breaking out what proportion are older versus younger.
Yes, so for what we'll have is for those 24 patients we will have all their data through at least two months.
And the last patients in for some of the patients that were started last year. We will have maybe six months of data, which will include BMD that were done at.
Entering interim time points, so that'll be a kind of a broad set of data we will look at different age groups and we haven't decided how much will we need to disclose we will have we are in Asia that are distributed around the age range that will allow us to look at different ages and use both PK and.
The biomarker modeling to try to deter.
Determine whether we need to increase the drug exposure at the lower doses.
Got it.
Thank you one moment for our next question.
Our next question comes from the line of Dae Gon Ha from Stifel. Your question. Please.
Hi, good afternoon, thanks for taking our questions maybe a question on Gtx 102 can.
Can you maybe provide any updates on the scoliosis patient has that patient resolve fully to continue receiving that dose and any update to the timeline of FDA submission package for the protocol harmonization. Thank you so much.
Yes, the patient as we've said before it resolved essentially resolved the problems. We had I think that we're continuing to evaluate him. He is not re dose yet we have to wait until his we will wait until as protein levels have resort resolved, which we will do at intervals and measure.
But we're encouraged how that's gone and the second question was.
Our ambition with FDA, yes, so we're planning that discussion shortly and.
We will be presenting at a price or how to approach moving ahead with expansion cohorts in the U S.
And.
We're expecting a good meeting we think we've gotten.
Good responses to discussions of them lately and I feel like there is an opportunity to move ahead, but we still need to have that formal discussion in order to open up the protocol in the U S, which we think will be important in being able to rapidly expand the study.
Put us in position to get a large enough amount of data to be confident about designing a phase III.
Thank you one moment for our next question.
And our next question comes from the line at least that Baker from Evercore ISI. Your question. Please.
Hi, there thanks for taking my question.
Could you run thrill.
With the change.
The royalty can you just remind us of that and how youre seeing kind of the net.
Profit from that changing as the royall key somewhat equivalent to what you'd be getting from the profit split.
That'd be helpful. Thank you.
Yes, so to be clear you're talking about the switch from a profit share with our partner Karen to the royalty period that correct. That's what you are talking about.
Yes.
Well in general that crossover will essentially.
B, even there won't be a significant change really.
<unk>.
The way we structured it originally made was actually pretty well modeled in terms of predicting what our share should be.
So the 29% the top tier of the royalty will cover.
And they expect to cover some commercial cost we are sharing some costs with them, but at this point. If you look at the total picture of how the.
The profit share was designed and how this is it's pretty flat pretty similar and so we feel.
Very good that you wouldn't see a significant step off or change in the revenue stream.
If there's anything more air and you don't want to say to that that was both summarize thanks Sam.
Thank you.
Thank you one moment for our next question and as a reminder, ladies and gentlemen, if you do have a question at this time. Please press star one on your telephone. Our next question comes from the line of <unk> Rama from J P. Morgan Your question. Please.
Hey, guys. Thanks, so much for taking my questions.
Two quick ones from me.
Following up on <unk> question on <unk> 111 million MTS III.
Is it a meeting with the FDA have been calendar and maybe walk us through the scenarios that could play out here and if you are able to go with an accelerated path forward for that program is there any read through to your broader gene therapy programs and then question two.
Maybe could you expand on the statement in the press release that Gtx 102.
There continues to be a dose and time dependent clinical activity in the population.
And then maybe if you could provide any type of color on what type of benefit you are seeing over what time period that would be helpful. Thanks. So much.
Yes, normally with regulatory authority discussions, we don't precisely put out exact timing of meetings and events that degree. The meeting is is is set and we're planning to meet with them shortly but.
Does the point of the meeting is that the FDA had already agreed on a clinical endpoint and with a longer period of time to evaluate.
However of late they have started showing some acceptance of heparin sulfate as a biomarker that is predictive and we believe in our.
Public discussion with Peter marks and in other settings that heparin sulfate marker maybe possible as the primary which would allow us to file earlier than waiting for the clinical data. So our discussion will focus on can we use heparin sulfate of the particular high quality assay, that's being used for purposes.
Filing with a commitment to complete the clinical follow up data of course to verify the clinical benefit.
So that will come.
Relatively soon.
And.
We'll let you know as soon as we know what the answer is to that question. It doesn't mean the program is it just means we can go faster. If we can go faster. It just allows us to file earlier, we still have to set up the CMC manufacturing pieces of the program and we're trying to run that is.
Capital efficient way as possible because we do have a lot on our plate.
So gtx 102.
We disclosed that there was some dose and time dependent differences, we have actually mentioned this before when you put out information earlier, we had talked about the fact that the quantitative endpoints around the Bailey.
We're better with the higher dose groups and with the lowest dose group at two <unk> in the U S. So that was the dose dependent piece and we've said that patient seem to improve over time and thats. The time dependent piece. So it's information we've been seeing it's in the the the main drivers are the ones, we've already disclose which are we're talking about in the bay.
<unk> scores and language and sleep.
And we're evaluating multiple things we're looking at many things, but we feel good about the pattern of response, we're seeing with both dose and time dependent.
And that's why we're moving into expansion cohorts.
Thank you once again, if you have a question. Please press Star then one one moment for our next question.
And our next question comes from the line of Joel Beatty from R. W. Baird. Your question. Please.
Great. Thank you.
For revenue are there any seasonal effects from Q4 of last year in Q1 of this year to be aware of.
Well there are always seasonal effects, but I think actually I think we did well last year in terms of hitting our marks.
Im not sure Ive area will have anything more to say, but I think you can always expect some lumpiness.
And particularly with Latin America, because the orders come in bursts.
And often on and so it's a little bit harder to predict is just part of the nature of the rare disease business, but I think things are well Eric did you have anything else to add on Lumpiness.
You covered it as far as.
Latin America is concerned I mean, I think it's important to recognize that we've had steady growth over the last five years for Christina.
It's established.
Gold standard for treatment of <unk>.
And we expect it to continue to grow as we've seen consistent increases in key performance indicators, such as patient finding start forms reimburse patients in unique prescribers.
Demand remains strong.
We do experience some seasonality.
The ordering patterns in Q4 and Q1.
Which has been consistent.
Year over year, if you look back over the previous years Q.
Q1, being a little lighter.
As expected as patients work through the reauthorization.
And changeable insurance process, just takes a little longer for them to get on.
But we remain confident in the underlying demand and which is why we reaffirmed our guidance.
Thanks, Eric.
Thank you one moment for our next question.
And our next question comes from the line that Youre, Ron Smith from Cowen Your question. Please.
Hi, guys. This is Brendan on for you Ron Thanks for taking the questions. Sorry can you just answered the phone cut out for just a second but for Christina.
I noticed.
Q4 sales related to jump up a bit.
If you can maybe give us any color as to what was really underlying that just in Q4 relative to Q3 at.
This is kind of some trends that youre expecting to hold forward hold moving forward.
And I just wanted to ask on Angelman.
I know theres a lot of questions here on adjusting anything but it does but can you just give us a sense of what we could expect in the next data readout in terms of really how many patients you're thinking to include whether they'll include them from the expansion cohorts and maybe over how long really kind of just trying to get a sense of where the internal borrowings for you. All in terms of when you want to put out the data.
Sure well I'll answer the <unk> question first and then.
Maybe Eric you can touch on the Chris fee and a strong Q4 question.
So in Angelman.
We've been releasing we've been doing these dose titration codes, which were just relatively small for patient groups, but it's clear we need to have something like at least 10 patients in each group to kind of give us.
The kind of data that we can do statistics on at least do enough projection to understand how to power a study.
So I'm looking for the announced to have maybe 20 patients or about half of what we need to enroll that's giving you a rough idea.
In addition, we would have the patients we have already treated who will have been titrated in maintenance mode and I would expect that would be the kind of volume of data that would allow us to accurately project.
What phase III would look like which is I think what investors asked for US is to have confident data that will allow them to see the future for the program in a phase III program, so that that end.
For Chris feed at Q4, I think it's a pattern we've seen before Eric perhaps you want to add to the pattern.
Yes, we had expected a strong second half of the year.
The work we were hampered in early 2022 with the only problem Barry we.
We saw continued increase in patient volumes in the offices.
More and more as well as participation and live educational meetings and programs.
And I think.
Consistently growing demand throughout the year.
Was one of the main factors driving the.
The strong Q4.
So it's a bit of a rebound out of hampered first part of the year, but as <unk>.
Generally has been strong in Q4.
Good.
Alright, alright, thanks, guys.
Thank you. This does conclude the question and answer session of today's program I'd like to turn the program back to Joshua Hager for any further remarks.
Thank you. This concludes today's call. If there are additional questions. Please contact us by phone or at IR at <unk> Dot com. Thank you for joining us.
Ladies and gentlemen for your participation in today's conference. This does conclude the program you may now disconnect good day.
Yeah.
The conference will begin shortly to raise and lower Johan during Q&A, you can dial star one.