Q1 2023 Ultragenyx Pharmaceutical Inc Earnings Call
Okay.
Good afternoon, and welcome to the Ultra genetics first quarter 2023 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 an opportunity to ask questions. During the Q and a portion of the call. It is now my pleasure to turn.
Turn the call over to Joshua Hugo.
This president and head of Investor Relations.
Thank you we have issued a press release detailing our financial results, which you can find on our website at ultra <unk> Dot com joined.
Joining me on this call our ammo caucus, Chief Executive Officer, and President Eric Harris, Chief Commercial Officer Air Combat Chief Medical Officer, Eric Olson Senior Vice President of corporate strategy, and finance and tax anger, 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'll now turn the call over to Emil.
Thanks, Josh and good afternoon, everyone.
In the first part of the year, we made meaningful progress were generating data from our key critical programs.
A phase II portion of the U S. One for <unk> III pivotal study for osteogenesis imperfecta is fully enrolled and the team has begun analyzing the data in advance of the data release in mid 2023.
Around that same time, we spend begin to begin and we expect to begin dosing patients in the randomized placebo controlled phase III portion of the study.
Based on the K O L feedback, we believe the phase III should roll swiftly and move us that much closer to a potential therapy for patients with this disease.
Similarly, with Gtx 102 phase one two for Asia, and we have begun ex U S dosing in the expansion cohort.
Outside the U S. We received positive feedback on our protocol and are activating multiple sites in Australia and across Europe .
This broadens the number of sites, who are experienced with gtx, one or two to support conduct of the phase one two.
And can participate in the future phase III study.
In the U S. We've had productive discussions with the FDA and look forward to possibly expanding dosing in the U S.
On the commercial side of the business continuing to grow revenue and make progress expanding access to our therapies around the world.
In the first quarter of 2023.
Chris Peter revenue in Latin America grew 120% to 20 million compared to 9 million in the prior year.
Five years into launch are still meaningful opportunities for significant growth.
We recently began the next chapter for Crow's feet in North America with Kyowa Kirin, assuming primary commercialization responsibilities for the program in the U S and Canada last week.
We will continue our joint commercial efforts in the U S through April 2024, and beyond that we'll continue promoting this blockbuster therapy to medical geneticists.
In the span of 10 years, Christina has moved through late stage development with approvals two rare genetic bone disorders and reach thousands of patients around the world I want to acknowledge the work and dedication of our integrated kyowa Kirin and <unk>.
And their commitment to the patient community and therefore their most recent average in planning for and achieving a smooth transition with patient experience is the top priority.
I also want to briefly comment on the recent Mark made by Peter marks proposing an operation Warped speed type approach to ultra rare disease.
This year marks a 40th anniversary of the orphan Drug Act.
It has been instrumental to progress in treating rare diseases and slept ultra rare diseases behind.
We have an opportunity right now to make progress.
Across many life threatening diseases afflicting infants and children for which there are currently no treatment.
Two our hope and our path forward to the parents and families of these children.
I'm awfully support of various part of the AC providing clear framework that makes et cetera approval pathway access will do therapies in ultra rare genetic diseases and.
And I'm hopeful that the agency will work with the urgency required.
Too many small companies with limited resources had to halt promising program, we greatly fear that we may lose the majority of these new treatments for ultra rare diseases.
I'm encouraged that the agency is showing receptivity and listening to the community.
Before I turn the call over to Erik Harris I'd like to welcome Eric <unk> to the call in his new position as Chief Medical Officer, and Executive Vice President.
Eric has been a driving force on our gene therapy programs and has extensive experience with rare metabolic disorders.
<unk> worked closely together for over five years on advancing our clinical programs and it has been a seamless transition as she steps into her new role as a full time strategic adviser.
Also want to thank Camille for her passion and dedication to both the ultra <unk> and the rare disease community. She has been instrumental in developing our clinical pipeline and I'm grateful for ongoing partnership going forward.
Now I'll turn the call over to Erik Harris to provide an update on our commercial efforts for the quarter.
Thank you Emil and good afternoon, everyone. In April 2018, we launched the suite in the U S with the hope of offering children and adults a breakthrough therapy targeting the underlying cause of their disease.
And the five year since we generated approximately $1 9 billion.
Cumulative topline product sales, which is shared with our partner <unk>.
Our patient finding efforts have led to nearly 3000 starts loans and approximately 2500 patients who have received reimbursed therapy.
When we launched Christina it was not well understood whether utilization by dose would be similar to <unk> and.
In the first quarter 2023, approximately 65% of the starts loans represented in adult patients.
And now they make up more than half, 55% in fact of all patients on reimbursed therapy.
This is one of the most important factors driving the success of this launch and yet there is still plenty of opportunities to continue growing this franchise.
The U S steels and patient support teams have executed well against the goal of bringing this therapy to pediatric and adult patients with <unk> and tio.
I am proud of their work, establishing a strong and growing base that <unk> with support from our extended transition team will be able to build on going forward.
We move on to the next phase I would like to thank the relentless efforts from our North American team.
That led us to be a very successful rare disease launch.
Yeah.
The team in Latin America has also made meaningful contributions to the overall success of Chris feeder as a reminder, this region is not impacted by the <unk> transition and we will continue leading all the commercialization efforts.
Our team continues to work country by country to obtain additional regulatory and reimbursement approvals.
Most recently, Mexico was added to the growing list of countries, where Chris meter has received a positive reimbursement opinion.
The Mexican Health Technology Agency has recommended the reimbursement for the pediatric patient population.
The opportunity for these patients to be treated with Christina.
In the first quarter 2021, there were approximately 120 patients on reimbursed therapy.
Over the last two years. This has grown to approximately 350 patients with the greatest acceleration happening in the last couple of quarters following pediatric reimbursement approval in Brazil.
As is common in this region ordering patterns drive some quarter to quarter variability in revenue.
The underlying demand is continuing to grow.
To date, we are reaffirming that Chris to meet our guidance, we issued at the beginning of the year the range of $325 million to $340 million includes all regions and all forms of course meet our revenue.
More specifically it includes Chris meter product revenue from Latin America.
And Turkey.
Cash and cash and noncash royalties from North America, and Europe , and the collaboration profit share revenue prior to the transition.
I'll now shift to the jewelry.
In the U S to leading indicators continue to show there is a real demand for this product from the patient community.
In the first quarter, we added approximately 35 completed start forms to the top of the funnel, which is one of the strongest quarters, we've had since launch.
As of the end of the quarter. There were approximately 400 patients on reimbursed therapy was approximately 200 health care providers, writing at least one prescription for <unk>.
Our early efforts to educate healthcare providers on the benefits of the dose titration supported by our clinical studies have begun to pay off.
We look forward to continuing these efforts to ensure patients are able to achieve optimal dose titration.
In Latin America, we are continuing to leverage our existing infrastructure to commercialize the Dolby.
Earlier this year, the first Brazilian patient navigated the injunction process to receive commercial therapy and in Mexico patients have begun receiving therapy through private insurance plans were.
We are continuing to work the authorities in Brazil, Mexico, and the other countries in the region to enable greater access to this important therapy.
Across Europe , the named patient and early access programs continued to drive demand for <unk>.
As we have said before France, and Italy are leading the way with more and more requests coming from Germany, Austria and certain middle East countries.
Across all regions, we expect Adobe revenue to be between 65 and $75 million.
Reaffirming the range, we announced at the beginning of the year.
We are also reaffirming our 2023 revenue total revenue guidance issued in the beginning of the year with a range of $425 million to $450 million. This range includes revenues for Chris Vita in digital.
Our ultra rare product <unk> as well as our latest commercial product FTR.
Before I hand, it over to Aaron's I'll once it I wanted to touch base on Ftes.
The European Canadian Japanese and Latin American teams have made meaningful progress in their efforts to launch FTE the outside of the U S.
And have received strong feedback from the Kols in those regions.
Throughout the year, they will continue filing the various country applications that will support the commercial launches that are expected to begin in the second half of this year.
With that I'll turn the call to earn 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 quarter ended March 31, 2023 totaled $100 million because of EDA revenue for the quarter was $76 million, which includes 50 million from North America 20 million from Latin America, and 6 million of noncash European royalty and other product revenue.
The jewelry revenue in the first quarter 2023 with $14 million of <unk> revenue for the same time period was $8 million.
Our total operating expenses for the quarter ended March 31, 2023, or $255 million, which includes R&D expenses of $166 million SG&A expenses of $77 million and cost of sales of 12 million.
Operating expenses for the quarter included noncash stock based compensation of $32 million.
In our press release issued today, we note that we have completed enrollment of the single ascending dose portion of the <unk> III phase one two study and that we have decided not to enroll patients in the multiple ascending dose cohorts at this time.
This was part of the company's decision to focus greater resources on our later stage programs and is not related to <unk> III product safety.
Similarly, we have deferred IND filings for certain early stage programs that were initially planned for this year to conserve and focus resources.
For the first quarter of 2023, net loss was $164 million or $2 33 per share.
We ended the quarter with approximately $750 million cash cash equivalents and marketable securities.
In the first quarter. There are certain uses of cash that do not repeat on a quarterly basis.
This is primarily attributable to the payment of our annual employee bonuses.
Additionally, Q1 2023 with our last full period, because we had a commercial cost sharing with kyowa kirin during the North America profit share period, and our funding of commercial support will be substantially reduced post transition we can.
Continue to expect 2023 net cash used in operations to be less than $400 million.
Now I'll turn the call to Eric <unk>, who will provide an update on our key clinical programs.
Erinn and good afternoon, everyone now I would like to provide brief updates on two of our key clinical programs.
<unk> 102 for the potential treatment of Angelman syndrome, and UX 143 for the potential treatment of osteogenesis imperfecta preferred turning the call back to Amazon closeout.
As previously discussed Angelman syndrome is a severe neuro genetic disorder with a broad spectrum of disease manifestations that affect multiple developmental domains. We have been treating patients with gtx, one or two for several years and have seen encouraging dose and time dependent clinical activity.
And the first part of the study we completed enrollment of patients in dose escalation cohorts.
To date, there have been 14 patients with at least six months of exposure to Gtx 102, including nine patients who had been on continuous therapy for more than one year.
Based on what we've seen in the dose escalation cohorts, we have now advanced to enrolling and dosing patients in expansion cohorts.
Which are designed to verify the gtx, one or two dose and treatment regimen that will be used in the phase III study.
Outside of the U S. We plan to enroll approximately 40 patients in cohort a.
Patients between four and eight years old in cohort b patients between 8% to 18 years of age patients in these cohorts will be dosed with what we expect to be the phase III dose and we will have the ability to individually titrate as a way to optimize the clinical benefit we expect to have the majority of patients enrolled in the <unk>.
Coming months.
In the U S discussions with the FDA are ongoing with the goal of harmonizing the dose strategy with the <unk> protocol.
The three patients who were originally treated in the U S have begun re dosing and continued to do well. We incurred we are encouraged that we are seeing clinical activity at these lower doses with a favorable safety profile.
Now turning to <unk>, three or <unk> the.
The truth I mab for the potential treatment of osteogenesis imperfecta Oi is a disease of mutated collagen and of abnormal bone metabolism.
We believe that bone strength can be nearly normalized without directly correcting the underlying college to effect. The antis Chlor Austin mechanism of <unk> provides a unique dual action to address the body maladaptive response to the defect of collagen <unk> stimulates osteoblasts to mature.
Took bone, making cells and makes hotels increased bone production, while also limiting the amount of bone resorption.
We are currently conducting a phase II study at that build on the substantial data morale at generated and we look forward to continuing the analysis and sharing the phase two data the phase II data are expected to include percent change in serum <unk> NP and safety data for all patients. It is also expected to include changes in.
CTX and the available three and six month lumbar spine bone mineral density.
We plan to use this data to help inform phase III dosing and show that we are on the path towards making stronger bone and bringing forward a much needed treatment for patients suffering with Oi.
I'll now turn the call back to Amy to highlight the key upcoming milestones and provide closing remarks.
Eric I'll summarize the key clinical catalysts before we open it up for Q&A.
I'll start with our gene therapy programs.
<unk> hundred one for GSD, one a dose the last patient in pivotal study earlier. This year. We're now in the 48 week window, we expect to share this phase III data in the first half of 2024.
<unk> 71 for Wilson disease is enrolling patients at dose finding stage. We expect this to complete in the second half of 2023 with data on safety initial signs of productivity expected in the first half of 2024.
Now dose multiple patients that had <unk> 301 phase III study and expect enrollment to pick up as more patients make it through the baseline screening period.
Discussion with FDA on UX 111 per sample leap, both <unk> syndrome are progressing and we're seeking a path towards <unk> review of this for this program.
Look forward to sharing more details with you when they are available.
Moving to <unk> III for osteogenesis imperfecta, the phase two portion of the study and fully enrolled and we expect to share these data.
And the transition to phase III would be in mid 2023.
Separately, we are planning to initiate a young pediatric study that compares the <unk> III to bisphosphonate.
Assessing fracture rates in a younger patient population, which have a much higher fracture frequency.
This study expected to begin later this quarter.
Lastly, gtx, one or two <unk> syndrome.
The long term exposure critical activity, Eric mentioned continue to support my belief, we have a therapy that could change the future for Angelman syndrome.
Our discussion with the FDA have been productive and we look forward to sharing our next data cut with you later this year.
We're making a lot of progress on our key clinical programs early in the year, Ralph investing today in our phase II programs with <unk> hundred 40, <unk> and Gtx, one too by establishing a broader network of investigators and study sites in more geographies.
Which will enable us to drive faster and more efficient phase III studies.
With that let's move on to your questions. Operator, please provide the Q&A instructions.
Thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please limit yourself to one question and one follow up.
Our first question comes from Gena Wang with Barclays. You May proceed.
Thank you for taking my questions I had two.
Two questions first one is for the.
I'll start with Genesis in the sector.
To update.
So would you be looking for to inform.
Optimal.
Three study design.
Related to the Phase III study design will patient baseline with two fractures per year would that be too low to show sufficient clinical benefit.
My second question very quickly on that.
Sure.
Chris' guidance to 325 to 340 minutes.
Julian.
Guidance for 2023 was that before or after 30% royalty to Omar.
Very good I'll go ahead and answer the Oi particular question and then.
I think the second part is really Erin can answer the question on how we're doing the royalty revenue.
So on OIS as to what are we looking for we're looking mainly the phase II portion is simply to help us fine tune the dosing.
We know the drug works and we know 20 milligram per kilo can work its dose. We're just trying to figure out whether the young patients might do better with a higher dose.
We normally expect that that exposure might need a higher dose to get to to achieve the same exposures older kids. So that's the primary purpose of it is just finding the dose number. The design is all set in the trial and the question second question you asked is.
As to practice peer enough of a threshold well first of all that's the minimum tender the trial. The average patient will have a number of fractures and we've done the work on powering in the design of the trial with 195 patients should have plenty of power to detect the fractured change.
And the key thing to recognize also the way we've designed the studies we will.
Comparing to placebo, we are going to look at an interim look and look at how the groups are operating and decide how long. The study should be follow how long the last patient who should be studied the total amount of time exposure for the first patients in could be 18 months or longer and some of the last one could be a year it could be 18 months and so the link.
The trial will help be adjusted based on the interim look to to determine.
Again to provide reassurance that you have the power our expectation though is that.
We treat kids with bone disease, they respond much more rapidly than adults. So our expectation is that the differential inbound will come relatively quickly.
As they did for example, with XL H treatment.
And the second part of the question is what is the forecast for Chris Vida and the interpretation with regard to the <unk> royalty.
The guidance of $325 million to $340 million is before the <unk> royalty share we continue to recognize all revenue although at certain portion will be noncash.
<unk> wrote for sure.
This is the way the accounting needed to be done the royalty streams. We've we've sold have a cap they come back to us and therefore, they looked at us that we are recording and reporting.
Noncash royalty income in addition to cash royalty income I still think it also gives you a better apples picture of what the royalty is I mean with the revenue is overall from the regency from compare year to year.
Okay. Thank you.
Thank you.
Our next question comes from Maury Raycroft with Jefferies. You May proceed.
Hi, Thanks for taking my questions.
For the Angelman program, just wondering if you could elaborate more on the feedback you received and then as the Registrational path dependent on dose harmonization or can you get alignment on key design considerations ahead of that data update.
Yes, so I assume youre talking about the U S feedback.
Just to guess that's correct.
Scott.
Well, we don't want to go through it in detail. What we said is productive meaning we're having a good conversation that's practical and looking at the issues, but we don't really provide detailed feedback on how it's going with what's being said until we get to the end to make a decision, but our goal here is to get.
To get the loading doses to be equalized in the regimens close in.
That we've said in the past we might try different regimens slightly different regimens, but I would look to try to get a program that is the.
A single path in loading and maintenance that we could run a phase III trial off but remember this is we're talking about the phase II section and from it we would derive what our phase III plan would be so I feel I'm encouraged we should be able to get this figured out and get to the right dose.
So on the Registrational.
Yes. The expectation is we're going to have one dose globally for load, but I will say one thing about dosing in rare disease in general as well as in Angelman. There really is no <unk> there is doses and the doses. We will have a range of response as always.
Our expectation those along with Angelman is that there will be some need for individual titration, we may prove the efficacy Ana.
Dallas, there may be some individuals that need higher or can get by with less.
And that will become part of it I'd point out for example, the work we did on Kuban for PKU, where we add one dose for the phase III study and then individual patients kind of titrate to their need.
Guide you to think that way the goal here in phase II those get to dose that we can load and have an important clinical effect and a large majority of patients and show.
The benefits of that treatment with the expectation in line with individuals may titrate to reach their optimal effect in their own particular situation.
Thank you Glenn.
Our next question comes from Dagon Howard Stifel. You May proceed.
Great. Good afternoon, thanks for taking our questions I'll ask a question on <unk> again.
Looking back in Australia, the bone biomarker data that's been presented previously wondering if you can comment on Tachyphylaxis, if thats, even appropriate and does Romo has recommended one year treatment duration have any implications on chronic therapy for us a truism that thanks so much.
Yes, I actually think you are.
What youre talking about its treatment. After a data is if you look at <unk>.
The peak of <unk> kind of go down and so it looks like youre, losing effect, but youre not really what's happening is you're losing the synchronization of the response.
It's like a pebble and upon the beginning of the response is very sharp start and then as each wave comes it settles in but if you look at the right dose at the end of the year you will see that you get a continuous steady pure <unk>.
Areas of the curve now is going up and the peak is less important than the area under the curve right. So you have to think of it as a.
The harmonic pattern essentially if you look at the Bummer density data differently, you will see the bone marrow density linear going up continuously for the entire year at 20.
Not at eight at Ada with fading a little more at the end of the piece, but at 20, they look continuous and it was ongoing at a good clip even at the end of the year.
So our view is that for this disease based on that information as well as the information from the withdrawal of a century of the mab the decline in bone mineral density indicate that theres, a strong reversal of the effect if you don't continuously treat.
And so our expectations that we will need to continuously treat beyond one year. It is possible that let's say after a couple of years thereafter, achieving some level of bummer density that is sufficiently strong than normal that you could back into let's say an every other month regimen or a maintenance regimen and we're going to continue to look at that as we go.
But right now we think <unk> different from osteoporosis as you do need chronic therapy, there's a stronger stimulus for resorption, there and we need to counteract that with continuous exposure and everything we've seen from master I would tell us that.
The continuous treatment will get you continuous bone production.
And so we look at these diseases being distinctly different for that reason.
Thank you.
Our next question comes from amount of <unk> Rama with Jpmorgan you May proceed.
Hi, Thanks for taking the question. This is actually a mountain kunal entre on a pump.
So looking ahead as it were.
Thing that you would be looking for in <unk> AD Comm panel next week that could read through to your broader.
Gene therapy program.
Well in our own I think the panels were looking at whether theyre going to give them accelerate approval honors the principles et cetera approval, maybe at test there and in addition to the specifics about their particular trial, we think.
Our approach is really important and rare genetic diseases. So we're supportive.
Approval, we don't think that approval cause other treatments or better treatments.
Developed we in fact think then Makoto approval for that program will help.
Further improvements in Duchenne muscular dystrophy be developed.
The panel needs to understand that.
From affecting our own program.
All of our programs have agreed upon endpoints with the FDA and Theyre, all really based on standard approvals into their combination of biochemical endpoints and other clinical endpoints, whether its removal of their drugs. Other outcomes. So our program is really not none of the three probe for those three programs are dependent on <unk> approval at this point in the end.
Points are set for what would be expected to be standard approval.
With regard to MTS <unk> in Sanfilippo program, there wasn't understanding about a clinical.
Based on our long term follow up approach to achieving filing, but we are evaluating that situation in the use of accelerated approval and heparin sulfate biomarker, we think thats. The right thing we think that situation is true for a number of companies and I think that a number of other companies have.
Treatments that reduce heparin sulfate and I think we'll be highly predictive of good outcomes. If the if you achieve a sufficient reduction and heparin sulfate. So there is maybe some.
Some meaning to that but I would say it is going to say more about throw up to duchenne than on whether <unk> or other other types of biomarkers will get approve but as a company. We're supportive of using et cetera approval pathway in rare diseases, and we think that.
We think that the FDA should not consider that to be a problem that should be an opportunity to treat more rare diseases than we've been able to treat.
Now that we have these novel precision medicine treatments available to us.
Great. Thank you.
Thank you.
Our next.
She comes from Joon Lee with true Securities You May proceed.
Great. Thanks for taking our question is on the efficacy signal.
You are seeing in the inkjet in the trial. So far what is your latest thinking in terms of approval endpoints is it still a CGI eas or something different and is that also part of their ongoing discussions with the FDA. Thank you.
Yes so.
I mean, what we've talked about before continues I mean, there's both.
Receptive and expressive communication are important and we're seeing improvements there and I think we're seeing improvements we said before in <unk>.
In fleet.
And I've actually several domain. So we see a lot of potential in any of these but since communication is important and if we were pushed into picking one we would pick the communication domain as being a unique and powerful one that's important to patients.
In my view the number of those domains are important.
You could decide on any of them, but at this point, our disguise with FDA have have not gone into the endpoints, we certainly touched on them.
Understand what we're working on and we expect to be able to get into that later this year with them, but right now our focus on getting the phase two open and understanding how to optimize our plan too.
<unk> opened the steady globally for the phase II portion of the engine program.
Thank you.
Yes.
Our next question comes from Yigal <unk> with Citi. You May proceed.
Hi, Tim This is Carly on for Yigal, Thanks for taking our questions.
I wanted to ask about the initial data for Wilson disease expected early next year I guess can you help put into context of what you plan to show and what you believe would constitute a positive outcome from from that part of the study. Thank you.
Yes.
The study just to remind you and I'll, let Eric touch on what we're validating. The study is basically looking at three dose levels right. So the study will look at three doses purposes part to pick the most effective dose, which we will look at a number of ways, but we have had a discussion with the FDA in.
It's a seamless design that is the phase II will lead right to the phase III and we have had discussion Eric touch on what our phase III approaches for the primary endpoint.
Yeah, great. So I mean fundamentally Wilson disease is a disorder of copper metabolism, and we can measure that in many ways.
Certainly with the clinical regulatory precedent that's been established that's important for us for us to understand so in addition to kind of the I guess, what I'll call a typical ways to measure copper. We are also looking at an activity based assay, which is measuring the actual loading.
Copper onto ceruloplasmin, that's important because the only way for that loading to take place is for the transgene to be producing that protein and for establishing the normal trafficking of copper will be also measuring <unk> plasma levels themselves if not.
<unk> two copper ceruloplasmin is quickly broken down so if we can show.
Increases in favorable stabilization or through a pile of them level. If that's another way to show that those trends gene is producing protein and were establishing the normal trafficking of copper. So again, we're looking to yes, correct. The toxicity of free copper, which key later is also due but also <unk>.
Correct, the functional copper deficiency, meaning that without the loading of copper onto a singular plasma and you are having a functional deficiency in the cells and tissues I need copper as a co factor for enzymes.
Thank you.
Our next.
<unk> comes from Yaron Werber with TD Cowen you May proceed.
Yes, great.
And interrelated question on Angel and also can you just give us a little bit of a sudden and the press release, you mentioned 14 patients have had at least six months exposure of nine with more than a year is that its a 14 make dose.
The only dose youre spending way now are there.
Full doses.
And secondly, when you were talking about next data update in the second half of this year is that going to be really safety only or do you expect to release some efficacy at that point as well. Thank you.
Yes, so remember in the extension patients say enter the load phase and they were loaded doses between really three three and a half to three 3% to seven and a half and then they are on maintenance between 10 and 14. So all of those patients on long term therapy are getting Q3 therapy at.
10% to 14 dosing alright, but the loading dosing is starting is actually lower than that that is the maintenance dosing during the maintenance period. So we haven't said what the dosing is in our current phase two expansion, we've decided to hold that information back.
We have a plan based on what we've learned from the dosing so far and we know you can load it will loaded a certain dose and maintain Ed.
Where it may rise to higher doses as we've seen in our other study in the first part of the study. The data later in the year will not just be safety or tenants put out information on the efficacy.
And.
So we're working through what will what we will provide and win.
From both the long term data in the.
Expansion cohorts separately.
Thank you.
Our next question comes from Chris <unk> Cuzco is K. There was Cheryl do you May proceed.
Hi, good afternoon, just considering the late stage nature and potential approval cadence around a number of your late stage candidates in the next few years I wanted to ask how you're thinking about leveraging and building on some of your ex U S and global footprint to address some of these markets where you mainly.
Right.
Well thank you so.
Commercially one of the benefits haven't commented with multiple approvals it does give us an opportunity to leverage that infrastructure.
And while we had.
Chris heat in certain territories, Latin America, particularly long term in Turkey currently.
Globally, we are dissolving mill savi.
And.
The brain, we brought in <unk> <unk>, primarily because we felt we could leverage our global commercial footprint.
More effectively by adding that especially in this gap between several approvals we had and then the next approvals and so they have Keith has sort of added another product to put in a launch mode X X U S. R. One of the things that advantage. The rare disease, you can launch relatively smaller teams of high quality people that can get a lot done.
And Thats key important being efficient capital efficient in how we do this and with the combination of product. We have we think we're able to leverage that if you think about the setup now having those three products globally and for products in South America, We're well set up then to be able to launch.
Several new products or other metabolic disease or expanding into neurologic disease. So I do think it sets up for what's important to us the real principle for objects from the beginning was that to optimally commercialize in gain.
Value you really need to commercialize globally, you can't just do you really need to get Poland revenue from globally. Once you've done all the work to develop an approvable product and so that's been our philosophy from the beginning and I think it's starting to pay off as we start to gain and grow revenue outside the U S.
Great. Thank you and it looks like you have a pretty significant presence at <unk>.
<unk> this year wondering if theres anything in particular, you think we should be focusing on thanks again.
Well, we've got a lot of programs, probably more gene therapy programs in phase III that anyone else is that true I think theres no one with more that I'm aware of so we also have a very strong political PCL platform and there is some information on the platform out there as well as well as about our new program <unk>, five which is the <unk>.
<unk> five <unk> gene therapy, which has some very.
Citing data in animal models, and even not even primates in pigs. So we feel good about our innovations and how to enhance delivery to the brain for our AAV nine gene therapy and that one will be coming to an IND. So that those data on that as well at <unk>. So we are we're busy there with all the technology in <unk>.
Alex who were working on.
Thank you.
Our next question comes from Jeffrey Hung with Morgan Stanley You May proceed.
Hi, This is Michael Rehaut answer Jeff hung thank you for taking my questions.
First one for Gtx 102, what are you learning during the maintenance phase, especially for the nine patients have been on for one year plus the further out you go has there been any evidence to suggest patients are building tolerance and can benefit from dose escalation.
A follow up.
Okay.
I think one of the key things to learn from made its first certainly mentioned long term safety. The fact, we're dosing so many kids chronically.
These dose levels is a very important piece of the story because.
If we were to have or any safety event that happens no matter how much drug you gave just needs a certain amount of drug to be accumulated than.
Then you might have a problem at some point in time and the fact, you can give the drug below thresholds and giving it. This way that you can do that means the drug can be given long term in chronically, which we think is important the thing thats more.
Even more interesting and important to understand that this is the development of disease and once we turn on their ability to develop it doesn't mean, they develop instantly they have to start developing whether its language or other things. It takes some time.
So what we've said is we are seeing time and dose dependent improvements, meaning as we watch people are gaining ground and improving and we feel like that gives us some confidence that we are working in a dose range that can be effective and that can change the future of these patients. So that's what we're learning from maintenance dosing both.
Long term safety and the ability to contract with dose drug and the fact that we can still we can see progressive gains.
That's very helpful. Thank you and then maybe just a quick follow up so for cosmic obviously, the clearest measure is going to be bone fracture rate, but what about bone deformation and pain. It seems that these are the clinically meaningful for these patients is there any ability to measure bone deformation and patients. Thanks, so much.
Well.
Sort of bound information is really tricky, we we did that kind of work and escalate redeveloped scales, we have readers and all that.
The problem is that it's not something that's going to help us with the regulators and while it may help patients to know.
Kind of thing is harder to power now with regard to pain and quality of life. Those are being measured in the trial were certainly managing their pain, but also chronic functional activity because we'd yesterday, where people are very fragile bones. They also don't feel good all the time, even if they don't have a fracture they have microfracture things go on and make them feel bad.
That caused them to not be active day sedentary et cetera. So we will be doing the kinds of quality of life.
Practical function assessments.
To support what the interpretation is on fractures.
So I appreciate you need to it's not enough just to look at fractures, but to look at the total case of an oi patient and learn more from them and we are doing that deformation of those one thing we'll look at the accuray to see them, but we havent formally went about a way to assess that I.
I do think Thats, something you would probably want to do in post marketing and particularly.
The most important thing really is to take a look at our one or two year olds that we treat and look how their bones are maintained versus deformed I think it would be strengthened their bonds than when therefore are five years old they could be dramatically different from what you'd see in someone who didn't have the right bone strength, who had fractures for several years instead.
So we'll look forward to that but I don't think thats lets say about the phase III that will be something long term and it's one of the main things. We've got into this program because we wanted to be able to change the future of these patients and we think starting young before their bodies are destroyed will be a great place to <unk>.
Change your future into kid that designated but wheelchair, but actually work and is it in chronic pain back should deliver real life.
Thank you.
Our next question comes from Joel Beatty with Baird You May proceed.
Great. Thanks for taking the question I'm, sorry, the GSD, one a gene therapy.
The agreement with FDA on the primary endpoint and are they're harder clinical endpoints that are being monitored that will be important for them.
Regulatory filing or commercialization.
Yes, we do have agreement on that we are using the reduction corn starch, while maintaining glucose control and that has been agreed to but the clinical efficacy will will not be just based on the primary endpoint alone there will be other secondary endpoints that will that will be looked at.
Part of the clinical meaningfulness assessment, but the primary endpoint in corn starch reduction was agreed.
Okay.
Thank you.
Our next question comes from <unk> Richter with Goldman Sachs. You May proceed.
Hi, Thanks for taking our question. This is Tommy on for solving sort of follow up on the Angelman question. How are you thinking about the interpret ability of this update in terms of efficacy maybe any details on months of exposure range of doses and cohorts would be helpful. Here and on OTC can you just comment on the pace of enrollment and any headwinds or tailwind there and when we could.
Data from this program. Thank you.
So on Angelman.
Yes, what we've heard and.
That we need to do is make sure when we put out efficacy data that we're putting it in proper context. So it's not only just dose and time exposure, but how does this compare to a comparable patient from natural history, and maybe to do a propensity score type of analysis, where you compare matched natural history patients to your patients to help create.
Greater confidence around the difference between the treated patients were doing and what you normally see in these patients we intend to do that the other thing is to calibrate the magnitude of change how big is that change what are the score mean clinically clinically is it clinically meaningful so that will be the second element of what we do well also.
For those patients of the original five that have been re dose we can certainly compare their results and how they did before and that will probably help give you some sense, but we are sensitive to the issue which is to make sure. We're providing you the proper context interpret the efficacy data effectively compared to what you would expect for these patients.
Next question was on the timing of <unk>.
<unk> enrollment and data expectations is that you were on OTC youre talking about the gene therapy.
Is that right.
Yes.
OTC, Okay, well that study is just is enrolling now it will depend how long we we put the GSD. One study is the primary driver on our gene therapy effort and.
Pushed back the OTC in terms of effort and drive it is enrolling now and we plan to be international study and the sites are open and there is growing interest so it should be enrolling this year.
But the timeline for that study is a little longer because the study is 64 weeks, it's not 48 for the timeline the data would be 64 weeks after last patient gets enrolled to that.
Obviously that means if we enroll even before the end of this year. The data will not be next year will end up being year after because of the longer timeframe.
Okay.
Thank you. Our next question comes from Doug <unk>.
<unk> <unk> with Guggenheim you May proceed.
Hi, This is Ryan <unk> on for Deb, Jay do you want to get your thoughts on the translate ability of <unk> NP correlations to DMD in the setting of postmenopausal osteoporosis.
Translated to pediatrics pediatric individuals with Oi.
Okay well.
We really don't have to worry about your process because there is enough asteroid data from <unk> and BMD. There were 90 patients at three dose levels had different doses of different <unk> responses in different BMD responses. So we actually have <unk>.
<unk> 90 pages worth of data to show the correlation what was what we found is that <unk>.
At one month is highly predictive of what you see at one year.
In these patients and that there clearly was a dose dependent on <unk> and that translate later.
The one.
And so what's interesting there is that.
How much <unk>, you're making is it really a measure of how much bone you're laying down but the way you respond at the beginning pretty much sets in plan in motion and <unk>.
<unk> will generate bone mineral density so we're pretty impressed how well they're correlated that said, we're also measuring BMD and our dosing study. So we will actually have some data through six months in some patients for the phase III study, which will allow us to do.
Directly confirm.
What are <unk> is telling us about dose with actual BMD data to so we'll have a little bit more than just the <unk> for our phase III in terms of understanding how to optimize the dose for our phase III.
Thanks for that.
Since in adults then translate to what you expect in the pediatric population is it sort of one to one.
Well one of the reasons to do this study is actually to determine how the adult response with <unk> relates to the Peds response, our expectation in fact that young patient will respond much more strongly that they have higher <unk> levels to begin with and Bill love a far larger surge because their bonds are metabolically more.
Active there.
The other question is.
Because younger patients have faster metabolism, they could clear the antibody faster and so we'd want to look at exposure to and so we'll look at how exposure correlates with <unk> and then we'll look at how exposure relates to age of the patient and the combination of that will tell us do young patients are they equally sensitive to adults at the same.
<unk>, yes, or no and and if they are then what is the exposure needed at different doses different ages and do young patients need more drug and so that would be the kind of tweaking that would help us assure that.
For your role really needed more antibody than the 12 year old that we can make that adjustment and give them the optimal benefit of the drug. So that's kind of the way we're looking at and hopefully that's helpful.
Thank you.
Our next question comes from Lisa <unk> with Evercore you May proceed.
Hi, Thanks for taking our question. This is Jamie on for Lisa My questions. So two for Maxim.
Provide some BMD data so how many patients worth of data should we expect and is there any correlation between bone marrow density and factually <unk> correlation. Thank you.
Yes. So we have 24 patients enrolled in the study and we would expect to have <unk> on all of them will have variable amounts of BMD data, depending how long ago. They were enrolled will have some six month data and probably more of a three month data in BMD.
In this group. So the question you asked and then follow up with <unk> predict fracture I think Oi at will.
From the asteroid study they showed a trend at the high dose, which was look consistent but they weren't enough fractures in the adults to be able to have enough power to tell so.
What we are.
Basing this on is the fact that the phones that are weak.
Can be restored and strength very quickly and the mechanism of how BMD increases with anti <unk> should be laying down bone, where it's needed where the bone is moving our whereas on stable. So just the very magna is alone means a BMD should predict well when BMD hasnt predicted as usually with catabolic anti catabolic age.
It looks like the phosphates, where youre just keeping bone wherever it is that it may not be in the right place. So when you make bone and lay it down in the right places. This mechanism. The Beaumont density will predict improvement in strength, whereas if you're just blockbuster absorption you ended up bone somewhere but it may not be in the right place and Thats why theres been some discrepancy in the past.
Anabolic agent like this.
We feel the bone strength will correlate it did well in the animal models.
That bone mass correlate very well with bone strength improvement, whereas with phosphate that wasn't true bone mass increase more than the bone strength did so I think there is enough data tell us that this mechanism will give us.
Our bone marrow density that is effective in improving bone strength.
Thank you. This concludes the Q&A session I would now like to turn the call back over to Joshua Hager for any closing remarks.
Thank you. This concludes today's call. If there are additional questions. Please contact us by phone or at IR at Ultra <unk> Dot com. Thank you for joining us.
Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
[music].
Okay.
Okay.
Yes.
Okay.
[music].
Okay.
Okay.
Thank you.
[music].
Okay.
Yes.
[music].
Okay.
Okay.
Yes.
Okay.
Yes.
Okay.
Yes.
Yes.
Okay.
Okay.
[music].
Okay.
Yes.
Okay.
Tim.
[music].
Okay.
[music].
Okay.
[music].
Okay.
[music].
Thank you.
[music].
Okay.
[music].
Yes.
Okay.
Yes.
Okay.
Okay.
Okay.
[music].
Yes.