Q1 2025 Ultragenyx Pharmaceutical Inc Earnings Call
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Speaker Change: Good afternoon, and welcome to the Ultra <unk> first quarter 2025 financial results Conference call.
At this time all participants are in a listen only mode.
Speaker Change: At the end of the prepared remarks, you'll have an opportunity to ask questions. During the Q&A portion of the call.
Speaker Change: It is now my pleasure to turn the call over to Joshua He got Vice President of Investor Relations.
Speaker Change: Thank you.
Speaker Change: <unk> issued a press release detailing our financial results, which you can find on our website at ultra Ganic Stockholm Joy.
Speaker Change: Joining me on this call or E Mail package, Chief Executive Officer, and President, Eric Harris, Chief Commercial Officer, Howard Horn, Chief Financial Officer, and Eric Combat Chief Medical 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 act.
Speaker Change: Results may differ materially.
Speaker Change: Please refer to the risk factors discussed in our latest SEC filings and now I'll turn the call over to him.
Speaker Change: Thanks, Josh and good afternoon, everyone.
Speaker Change: First quarter, we continued to make meaningful progress across one of the most productive commercial and development pipelines in rare diseases.
Speaker Change: Our commercial team delivered a strong quarter that puts us in a position to have another year with meaningful revenue growth.
Speaker Change: Our early investments in high performing teams have helped generate substantial revenue growth, while we commercialize their products outside of the United States.
Speaker Change: At the same time, we are preparing to launch our next set of programs in the U S and around the world.
Speaker Change: Our development teams and advanced our large and late stage programs as well.
Speaker Change: For the U S 143, and osteogenesis imperfecta patients in the PC space have now been enrolled for at least a year in the process begun to clean and lock the database for our second interim analysis.
For Gtx, one or two in Angelman syndrome phase III is enrolling efficiently at sites in the United States, Canada, Japan, Germany, Poland, Spain and data are expected in 2026.
Speaker Change: For <unk> 301 in ornithine transcribed families deficiency or OTC. The phase III study completed enrollment of the first quarter and is on track to read out data over the next year.
Speaker Change: But you had 71 Wilson disease. The study is now enrolling the fourth co. Joseph does finding cohort that will enable dose selection and transition to the pivotal stage.
Speaker Change: At the same time, we're working on two separate BLA is one currently under review in the second to be submitted.
Speaker Change: The Gtx 401 for GST won a BLA submission is on track for mid 2025. After successfully completing the P. P. Q runs qualification lots essentially at our manufacturing facility in Bedford, Massachusetts.
Speaker Change: The U S 111 for Sanfilippo syndrome BLA under review by the FDA is progressing on schedule as expected.
Speaker Change: It's not our standard practice to go into the details of Reg to interactions, but I think it's meaningful at this current time for investors to be aware that our interaction with the FDA on the UX 111 billion, thus far remain on track.
Speaker Change: Last month, we had our mid cycle review meeting that occurred on the standard timeline. We also know the inspections of the manufacturing facilities and clinical sites have been scheduled according to normal cadence and are currently underway.
Speaker Change: We remain on track for the produce the action date of August 18.
Speaker Change: Going forward, we don't plan on giving the details of all our regulatory interactions, but we did want to share enough detail for you to remain confident you are that the U S. BLA review is progressing according to plan.
Speaker Change: With that I'll turn it over the rest of the team to share. The details of why 2025 will be a transformational year for all genetics, Eric I'll hand, it off to you to go through the commercials team's execution in the first quarter.
Eric: Thank you Emil and good afternoon, everyone.
Eric: In the first quarter the commercial organization to continue building on the momentum that we saw at the end of 'twenty 'twenty four.
Eric: Starting with Christina in Latin America, where we lead commercial operations. Our team generated approximately 40, new start forms that led to approximately 40 patients on reimbursed therapy.
Eric: We now have approximately 775 patients on commercial product in the region as the team continues to exceed our expectations for Christina.
Eric: Physicians in the region consistently tell us how well that patients still on therapy, which has led to an increasing number of doctors writing prescriptions for multiple patients.
Eric: We expect growth in the region to continue following the successful negotiation of reimbursement from the Brazilian and Mexican authorities, which are the two largest payers in the region and continued expansion in other central and South American countries.
Speaker Change: In the United States, our partner he our Karen is leading commercialization for Christina.
Speaker Change: First quarter 2025 revenue was supported by increasing new start forms and new patients on reimbursed therapy.
Speaker Change: It is fulfilling to see that adults.
Speaker Change: Around.
Speaker Change: Adult demand it is fulfilling to see that adults around.
Speaker Change: Adults.
Speaker Change: Or have <unk>.
Speaker Change: The makeup.
Speaker Change: Makeup more than make up more than half of <unk>.
Speaker Change: Patients on therapy, considering the skepticism around adult demand at launch with <unk>.
Speaker Change: <unk> 2025 U S. Christy that revenue to continue growing as they work to identify new pediatric and adult patients with X L H and convert them to treatment.
Speaker Change: Moving on to the jewelry and the United States growth of new start forms in the first quarter continued to steadily increase just as we have seen in prior quarters. Our team generated approximately 30, new start forms and added approximately 25, new patients to reimbursed therapy.
Speaker Change: This brings the total since launch in 2022, almost 600 patients on reimbursed therapy, the split between pediatric and adult patients continues to be approximately 65% piece and 35% of adults also the number of new prescribers continues to grow in the first quarter.
Speaker Change: With approximately 270.
Speaker Change: Unique prescribers.
Speaker Change: For <unk> across the EMEA region. They are over 260 patients treated under named patient sales across the region.
Speaker Change: The majority of demand is from France, but we are receiving an increasing number of requests from other countries within the EMEA region, including the middle East.
Speaker Change: The demand for this product is quite strong in this region, especially given we are not actively marketing the therapy and simply responding to named patient requests.
Speaker Change: I'll close with a few comments on our skis, there, which we began commercializing in our territories outside of the U S in 2023 and.
Speaker Change: The EMEA region, we have patients on reimbursed therapy for the majority of major countries. We now have treated approximately 250 patients, adding more than 50% since the beginning of the year across 15 countries in the region.
Speaker Change: This is a result of our commercialization efforts in response to named patient requests as we continue to successfully navigate the country by country pricing negotiations.
Speaker Change: In Japan. The team continues to build on the launch momentum following the pricing and reimbursement approval that we received last year in Canada. We are continuing pricing negotiations with government health authorities and have secured reimbursement agreements with three of the four major.
Speaker Change: Private insurers over time.
Speaker Change: We expect <unk> revenue to contribute more meaningfully to total revenue as we continue successes to successfully launched this important products outside of the United States.
Speaker Change: As I have mentioned on previous earnings calls, we continue to expect quarter to quarter variability in revenue.
Speaker Change: Primarily due to uneven ordering patterns for Chris feeder in Latam, but we remain confident in the growing underlying demand for all of our products around the world with that I'll turn the call to Howard to share more details on our financial results and guidance.
Thanks, Eric and good afternoon, everyone I'll focus on first quarter 2025 financial results and guidance for the year.
Speaker Change: Starting with revenue.
Speaker Change: In the first quarter of 2025, we reported $139 million, representing 28% growth over the first quarter of 2024.
Chris Vida: Chris Vida contributed $103 million, including $41 million from North America, $55 million from Latin America, and Turkey, and $7 million from Europe.
Chris Vida: In total this represents 25% growth over 2024.
Chris Vida: If you focus on Latin America, and Turkey, where we are responsible for generating sales. This represents 52% growth over 2024.
Chris Vida: Turning now to the JV contributed $17 million consistent with its expected steady growth trajectory.
Chris Vida: <unk> contributed $11 million as demand continues to build following launches in our territories outside of the United States.
Chris Vida: And <unk> contributed $8 million as we continued to treat patients in this ultra rare indications.
Chris Vida: Total operating expenses for the quarter were 282 million, which included R&D expenses of $166 million SG&A expenses of $88 million and cost of sales of $29 million.
Chris Vida: Operating expenses included noncash stock based compensation of $40 million.
Chris Vida: For the quarter net loss was $151 million or $1 57 per share.
Chris Vida: As of March 31, we had $563 million in cash cash equivalents in marketable securities.
Chris Vida: Which reflects $45 million in cash payments made for two milestones during the first quarter of 2025 that were achieved in the fourth quarter of 2024.
Chris Vida: Specifically $30 million for a Gtx 102 phase III study milestone and $15 million for an FTE as a sales milestone.
In the first quarter of 2025 net cash used in operations was $166 million.
Chris Vida: Recall in the first quarter of the year, we typically use more operating cash then in the subsequent three quarters because it includes items like the payment of annual bonuses.
Chris Vida: In addition, first quarter net cash used in operations also included the $30 million Gtx 102 development milestone payment I mentioned earlier.
Chris Vida: Net cash used in operations is expected to decrease in the remaining quarters of this year and is expected to total less than what we used in 2024 as we continue on our pathway to full year GAAP profitability in 2027.
Chris Vida: Shifting to revenue guidance for 2025, we are reaffirming the guidance we gave in February.
Chris Vida: Total revenue is expected to be between $640 and $670 million, which represents 14% to 20% growth over 2024.
Drivers include increasing demand for our products in Latin America.
Chris Vida: <unk> penetration of the pediatric and adult XL each markets in the U S and growth for <unk> in Europe and Japan.
Chris Vida: Chris Media revenue is expected to be between $460 and $480 million, which includes all regions and all forms of crispy the revenue to ultrasonics.
Chris Vida: This range represents 12% to 17% growth over 2024.
Chris Vida: The <unk> revenue is expected to be between 90, and 100 million, which represents 2% to 14% growth over 2024.
Chris Vida: As in prior years are to jewelry projections represent a blend of faster growth in countries, where we commercialized and lower growth in countries, where we respond to named patient requests.
Chris Vida: Lastly, with respect to tariffs the landscape continues to evolve.
Chris Vida: We are actively monitoring and evaluating multiple potential scenarios.
Chris Vida: Based on what we see currently we do not expect to have a material exposure for any of our products, including Christina.
Chris Vida: With that I'll turn the call to our CMO, Eric <unk>, who will provide an update on our key clinical data readouts expected this year.
Speaker Change: Howard and good afternoon, everyone I'll provide some brief operational updates on our late stage programs and review our upcoming clinical milestones starting with <unk> three for the treatment of osteogenesis imperfecta. The phase III orbit study continues to progress well and as we noted earlier in the year the safety profile as <unk>.
Chris Vida: <unk> 12 is observed observed in phase II.
Based on the phase II data. We previously shared we are confident that the study will show a clinically and statistically significant reduction in annualized fracture rate at either the second interim or final analysis.
Chris Vida: Orbit in Cosmic studies will both have an interim analysis midyear. After all patients have been on therapy for at least 12 months. The data readouts will be led by or bet, meaning that if orbit clear as the P value threshold of less than <unk>. One we will look to see a cosmic has cleared the same P value threshold of less than point online.
Chris Vida: Progressing to full study completion in the fourth quarter of this year Cosmic will also continue to a data read out to align with the orbit data readout with outspending Alpha at this interim assessment.
Moving to Gtx 101 for the treatment of Angelman syndrome.
Chris Vida: We have set an ambitious goal of enrolling a 120 patient pivotal study in less than one year I'm proud to report that we are on track to achieve this goal and we are actively working with sites in the U S Europe and Japan to enroll patients. We have also made progress finalizing the Aurora protocol, which will study younger and older.
Chris Vida: Their patients and those with other mutations we expect to take this protocol through the regulatory process and begin enrollment later this year.
Speaker Change: <unk> D. TX for 401 for the treatment of glycogen storage disease type One act and.
Speaker Change: In our press release today, we shared some of the additional crossover data that will be included in our BLA filing midyear.
Speaker Change: During the crossover period patients demonstrated even greater reductions in total daily cornstarch at their last visit compared to baseline in both the ongoing <unk> hundred one group and the placebo crossover 50 checks for one group pace.
Speaker Change: Patients in the <unk> group demonstrated a 60% reduction in daily cornstarch at their last visit with a mean follow up of 120 weeks. This is a substantial and continued reduction compared with a 41% reduction in daily Cornstarch observed at week 48.
Patients in the placebo to Gtx <unk> group demonstrated a similar 64% reduction in data cornstarch at their last visit.
Speaker Change: Where the mean duration on therapy with <unk> hundred one was 69 weeks patients in both groups have demonstrated statistically and clinically meaningful reductions in daily cornstarch requirements demonstrating continued benefit from this gene therapy over time.
Speaker Change: <unk> also continues to demonstrate a consistent and acceptable safety profile with no new safety signals identified.
Speaker Change: The manufacturing process at our Bedford, Massachusetts facility is going well and we recently successfully completed our process performance qualification runs while the tech transfer from <unk> to our facility was done quickly and efficiently. It did impact our BLA submission timing, we were able to capitalize on this opportunity.
Speaker Change: <unk> to collect more clinical data, resulting in an even stronger clinical and CMC filing package that we will submit to the FDA mid year. Finally, I'll touch on the <unk> 701 for the treatment of Wilson disease as noted in our press release today, we have recently began enrolling patients into a fourth dosing cohort.
Speaker Change: At a dose of 40 <unk>.
Speaker Change: These patients will receive a new immuno modulation regimen with Rituximab in tanker alignment. In addition to the corticosteroid Roger menus in the previous cohorts, we expect that the combination of enhanced immuno modulation regimen and a moderately higher dose could achieve the broad response needed to select a dose to take forward.
Speaker Change: Into the pivotal stage two of this study.
Speaker Change: Also noted in our press release today, the pivotal stage two portion of the protocol was amended to a 52 week randomized open label active control design. The open label design allows for patients and investigators to be more comfortable with discontinuation of standard of care consistent with our experience and our other metabolic gene therapy probe.
Speaker Change: Graham.
Speaker Change: The stage two primary endpoints are largely the same as before but instead of comparisons to placebo. They are now compared to the active control arm.
Speaker Change: Specifically, we will be looking at the change in 24 hour urinary copper from baseline to week 52 and percent reduction in standard of care by week 52, I will now turn the call back to Amy to provide some closing remarks.
Amy: Thank you Eric.
Speaker Change: First part of the year, we've made tremendous progress executing on all fronts.
Speaker Change: Patients in both U S 140, <unk> for US just imperfecta studies have now been enrolled for at least 12 months and this enables our teams to start the process of cleaning and locking databases will that will be shared with the data monitoring committee in the next few months.
Speaker Change: Feedback, we hear from investigators with patients in the phase II portion of the orbit study gives us confidence the treatment effect with <unk> and osteogenic Superfecta is transformative for these patients.
Speaker Change: In closing, we expect 2025 to be the most productive year in our company's history with the commercial organization generating $640 to $670 million in revenue and the development organization managing one BLA under review secondly submitted in the middle year and multiple phase II studies enrolling a reading out data we are in prime position to lead the future.
Speaker Change: <unk> of rare disease medicine.
Speaker Change: Let's move on to your questions.
Speaker Change: Operator, please provide the Q&A instructions.
Speaker Change: Thank you we will now be conducting a question and answer session. If you'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May press star two to remove your question from the queue for participants using speaker equipment may be necessary to pick up your handset before pressing the star keys.
Speaker Change: In the interest of time, we ask that participants limit themselves to one question and one follow up and re <unk>.
Speaker Change: Enter the queue for additional questions one moment please.
Speaker Change: Poll for questions.
Speaker Change: Our first question is from your on Werber with TD Cowen.
Speaker Change: Great.
Speaker Change: Thank you so much for taking my question.
Speaker Change: Not surprisingly it is going to be about such with some of the second interim analysis and sort of one <unk>.
Speaker Change: In two parts, maybe the first one you.
Speaker Change: You've talked recently about dispersion in the study and that's something that when we look at the prior data in the phase two the dispersion is not really shown we can tell is there is variability in how many factors patients have a baseline. So can you maybe explain to us what do you mean by dispersion and maybe why it's important and then secondly, when we look at the <unk>.
Speaker Change: 67% factual reduction if I recall correctly that was at around six to seven months can you give us a sense kind of what he was saying when he was at 14 months. The latest cut that was at ASP EMR. Thank you.
Speaker Change: Sure round. Thank you. So I don't I don't know if I actually use the word dispersion that's like a statistician term.
Speaker Change: Usually mentioned variation that there is a variation in their in the analyzed fracture at baseline and.
Speaker Change: We know we have people that can have more than three fractures, a year any flat fractures rate of greater than three and some less well we stratify the trials that those with a greater than three would be stratified equally between the treatment and placebo groups as would the ones below that but how is this JV that it can have some impact on the problem.
Speaker Change: Success, just because variation is what really affects P value. So we haven't talked to that distribution are shown it but there is a fairly wide range of fractures baseline now. This typical method, we're using the negative binomial will capture.
Speaker Change: The <unk> at baseline as a co variable, meaning will help correct for that in the way we analyze it.
Speaker Change: Which help assure that doesn't have a substantial impact. We're also stratified by age in the trial. So we're doing a number of things, which will help reduce variation, but there is a lot of variation in severity and fracture frequency and we think we've done what we can but that might be one reason why you might not hit <unk>. We think we have a good shot of hitting <unk> based on everything we know.
Speaker Change: But we are very strongly positive on their trial, whether at IAG already and that's going to be successful. So let's talk about the fracture reduction we announced phase III data at the after six months or so and showed a 67% reduction with a P value point out for now.
Speaker Change: And when we did the 14 months how does the same 24 patients we had the same 67% reduction in fracture frequency median.
Speaker Change: And the P value, though was point <unk> one four.
Speaker Change: So you might be wondering well half of the number of the same I would look at this is think of it as a line of accumulated fractures. The accumulated fractures and one group is going up at a steep rate and the slope of the other line is is only.
Speaker Change: 67% less right. So the two lines are running at.
Speaker Change: Apart from each other if you cut those two lines earlier theyre not as far apart, but if you wait for those two lines to progress further there further apart the slopes are still 67% the same treatment effect size.
Speaker Change: But the P value is better so what's happening at interim one is that they may not have separate far enough yet and it would only it would have happened if we had a lot of fractures.
The second time, we will have run longer than we should have much better separation. So from that analysis access. It suggests that we could hit it <unk> its a reasonable shot.
Speaker Change: Now we are we did do an analysis of our phase II data for those that have heard this from me.
Speaker Change: We did take the same data analyzed patients as if their prior year was on.
Speaker Change: Placebo and compared to their current year on treatment and with the negative binomial you'll get the same 60 mid 60% kind of reduction.
Speaker Change: And alright with good P Valley, So just to be clear if you do it by the method we're using in phase III you get a very similar result, just simply wanted whether the different statistical approach would matter.
No.
Speaker Change: Variability is an issue dispersion of statistical version of it we could go into but I think the key thing I would say is that we I think we have plenty of power to succeed in this study, whether it's <unk> or at the end.
Speaker Change: Alright, it was gone.
<unk> Ahmad: Our next question is from <unk> Ahmad with Bank of America.
Ahmad: Hi, good afternoon, Thanks for taking my question.
Ahmad: I also have a question on ally, but this would be if the study moves to a third interim read.
Speaker Change: What's your view of the likelihood of success, you've talked now multiple times of our confidence in the molecule overall and we would agree that the drug is active but if the study.
Move to the third interim what would be a reason to be concerned that it would not work at the third interim thanks.
Speaker Change: Great well it won't be the next assessment as the final assessment for the study and that P value threshold will be <unk>.
Speaker Change: So it would be.
Speaker Change: A lot easier to hit <unk> four so.
Speaker Change: We think that we will hit one or the other based on our experience of what we've seen.
Speaker Change: I don't think we could miss the point out for at that point with 18 months of time.
Speaker Change: But it's always in rare disease programs. The other thing you always are battling as variation.
Speaker Change: Variability in patients.
Speaker Change: But based on the the profound difference in bone marrow density change that we see that happens within two to three months and the fracture rate effect happens within two to three months, we feel pretty good about hitting but confident about.
Speaker Change: Overall, the study hitting at even at the end if not at the <unk>. So I can't tell you. The reason why variation is always a thing that.
Can create complexities, but given that the patients the program was 159 patients.
Speaker Change: It's a pretty large study and the data were talking about before it was 24. So I think we've got a lot of power in there but.
Speaker Change: And we've done everything we can to manage variations.
Speaker Change: Feel good about we'll hit it this year either a point on one or <unk> four after 18 months.
Speaker Change: Okay.
Gena Wang: Our next question is from Gena Wang with Barclays.
Thank you for taking my questions, maybe all of them.
Switch gear.
Gena Wang: All of the keynote.
Gena Wang: A fundamental question I think really the reasons seaborne nomination.
With many Prasad I think are doing lots of uncertainties, we saw massive selloff.
Gena Wang: All tech sector, and so Jamie wanted to get your thoughts like.
Gena Wang: Where do you see that could be potential impact too.
Gena Wang: Too specific in the rare disease space and how would you.
Gena Wang: Ill deal with or what will be the strategy you have dealing with this situation and do you still open questions on lots of uncertainties there.
Gena Wang: And my second question is also go back to the Hawaii I think recent discussion. We had you did mentioned that I think over maybe 80% of patients baseline Bisphosphonate and then the washout period in <unk>.
Gena Wang: Enrolment you.
Gena Wang: You did a skip the washout period, so would that be and concern.
Gena Wang: Or do you see the placebo fractionally picking up at some point, but that has a delay rather than.
Gena Wang: <unk>.
Gena Wang: <unk> months, what do I need to look at longer time, so that we can see the placebo arm factor when you start to pick up.
Gena Wang: Very good so yeah, the CBR appointment.
Gena Wang: We don't think it was a good choice as someone who has argued against et cetera approval for cancer program.
Gena Wang: That may be a concern I think we'd have to anchor back to the fact, the carry has been talking about the importance of rare disease approvals and thinking how to improve and accelerate the process to reduce the time and development. So we'll have to anchor to that discussion.
Gena Wang: A discussion point, he's made and see what <unk> does I think for our own program for <unk> hundred 11, we have lots of clinical data in the program.
Gena Wang: I'm less concerned about it because in fact, we have clinical data showing efficacy in addition to the <unk>.
Gena Wang: Biomarker data.
Gena Wang: And so I think for US right now we're not concerned I think for industry at large it would be important for exciting approval will be available for a lot of the gene or cell therapies.
Gena Wang: And importantly, <unk> carries public commitment to try to move these things forward is something that we follow through on that.
Gena Wang: How prasad will do that we don't know but.
Gena Wang: Okay.
Gena Wang: I think the FDA is very important in the industry supports FDA and their mission and we just hope that.
Gena Wang: They continue to make good decisions.
Gena Wang: On the second question.
Gena Wang: So more native Saturday to 89% or something like that we're on this fascinating the steady rate.
Gena Wang: <unk>.
Gena Wang: The washout timeframe is in the one to two year period. So we would expect the placebo patients to be have steadily declining frac.
Gena Wang: Frac.
Gena Wang: This phosphate effect and therefore are steadily potentially increasing fracture rate as their bone marrow density has declined.
Gena Wang: But.
Gena Wang: We don't think that effect is really a meaningful effect compared to the dramatic effect on bone marrow density that's going to happen with the treatment right.
Gena Wang: So the $5 12 group, we had a 29% increase the bummer density improvement.
Gena Wang: The effect on the other groups will not be nearly so large so what it would do with both crews would have a loss of this moth this phosphate effect over the period, but remember the treatment arm will also have some anti resort for effect from the drug itself. So if anything what this will do is increase the rate of separation as time.
Gena Wang: On and improve the power of the study longer it goes.
Speaker Change: Do you have anything else to add to that just like we didn't count on this when we were designing the study and powering. The study we did not account for that effect so any <unk>.
Gena Wang: And that.
Gena Wang: That could be considered an upside.
Gena Wang: Yes.
Gena Wang: Very good thank you.
Gena Wang: Okay.
Speaker Change: Our next question is from <unk> Richter with Goldman Sachs.
Speaker Change: Hi, this is with yonker Shelby and thanks, so much for taking our questions and congrats on all the progress.
Speaker Change: Maybe another one on <unk> could.
Speaker Change: Could you just discuss how you plan to message the outcome of the interim to the street.
Speaker Change: Whether you intend to share any data with this update thanks so much.
Speaker Change: Yes.
Speaker Change: The.
Speaker Change: D&C is presented the information on orbit.
Speaker Change: If it is positive that will inform us and.
Speaker Change: We will inform the street of the results.
Speaker Change: The if they if the pharmacy at the store.
Speaker Change: <unk> needs to go to the end we will also.
Speaker Change: Inform the street that the study is continuing to the end. So if you haven't heard from us because of the decision hasnt happened yet.
Speaker Change: A decision either its moving forward to the final assessment or it's ending at the interim will be clearer. We haven't set what all the data that might be in or not in that release, but different from interim one we are having to fully clean the database for a potential filing from that dataset. So the timed data would be faster than we have.
Speaker Change: Said for the <unk>, one where we had only partial lock in we had to continue the trial. So it would be relatively soon after we talked about data and now if I II is positive then.
Speaker Change: Or the <unk>.
Speaker Change: Cosmic study will be evaluated orbit is negative then we won't on blind the cosmic data won't wait for both studies to go to the next assessment.
Speaker Change: Okay.
Speaker Change: Thanks, so much.
Speaker Change: Our next question is from <unk> Rama with Jpmorgan.
Speaker Change: Hi, Thanks for taking the questions is actually now can kudo entre autopilot.
Speaker Change: Where are you on your enrollment curve for the Angelman program and have you opened all of the global sites for the program yet.
Well I'll ask Eric to comment on that yes. So like we said our plan is to fully enroll that study. This year. We are committed to that we have really prioritize that and leveraging the experience we have with Oi and really enrolling.
Speaker Change: For us for rare diseases are relatively large pivotal trial. So we are certainly.
Speaker Change: We want to do this as quickly as possible and yes, our global sites are active and beginning to screen and dose patients.
Speaker Change: So all sites active.
Speaker Change: Excellent. Thank you.
Speaker Change: Our next question is from Kristen <unk> with Cantor.
Speaker Change: Hi, Good afternoon, you talk about potential variation factors I wanted to see.
Speaker Change: Color about how youre thinking about the age of the baseline I know investors tend to focus a lot about the type.
Speaker Change: Types of Oi, but based on some of the BMD data you've shown.
Speaker Change: Sachs could be even superior the younger you treat and I know the orbit trial has a range of about 20 years. So is there anything you're able to share.
Speaker Change: I don't think we shared the exact enrollment, but the majority of patients are going to be pediatric and a relatively limited number of older patients we are including them in order to allow us to label for adults as well off that study if there's any question.
Speaker Change: The majority of the patients are going to be in the pediatric age range for the program is there anything else you think we could offer Eric.
Eric: No I think that covers us.
Speaker Change: Thanks, and then just to clarify if IAG is if it does hit the analysis will you also be announcing the same day, whether cosmic with successful as well or will those updates be suffering. Thank you again.
Speaker Change: Yeah, we haven't said it depends they they're not happening the reviews of both programs are happening the same day, one will happen and then the others. So.
Speaker Change: We haven't said yet whether we would have them both at the same day or not.
Speaker Change: We'd like to keep you guessing a little bit right, if I make it too easy.
Speaker Change: Our next question is from Yigal <unk> with Citi.
Speaker Change: Hi, Thanks.
Speaker Change: You commented at all on the distribution of the types for ROI for one three and four.
Speaker Change: Phase two versus the orbit trial and then also this is a very specific question, but what exactly is the tolerance on these P. Values mean, we're talking about some pretty small numbers here. So I mean hypothetically if it's like point of one one.
Speaker Change: On the second interim is that is that a sale or when it's I mean, I would I think I know, but I'm not sure actually so I was just curious if you could clarify that level of detail on whether you were ever told the P value for the first one the first interim.
Speaker Change: So on the OLED types I think we have disclosed before that in the in the phase II study there were seven type threes and fours and 17 type one.
Speaker Change: And then.
Speaker Change: Because it <unk> really impressed with the results and they were interested in bringing in.
Speaker Change: More of a severe three and four patients. So we ended up with more type threes bought half the patients are type three and four are approximately there in the study. So it's definitely an increase in type threes and fours in the phase III study than they were in the phase two study.
Speaker Change: Alright, now for tolerance, we haven't set that like how many sig figs of significance.
Speaker Change: Honestly I don't have an answer for you, but I would say if as I pointed out <unk> five or <unk> six that is not lessen pointed out one right so that would probably.
Speaker Change: That would be considered a miss at this point, which means you can be very close to a very good result, and still Miss and go to the end of the year, which is why we shouldnt overreact, if there was an issue but.
So that's the basic the tolerance question and then.
Speaker Change: The last one was a there was a P value and the others we haven't.
Speaker Change: Provided a pea that we were not aware of the PD one nor provided one in the interim the first Aaron we were just told that it was.
Speaker Change: Steady was continuing and that will result.
Speaker Change: So what we know from.
Speaker Change: The prior analysis of phase two though is that the P value was.
Speaker Change: 0.14.
Speaker Change: At 14 months so.
Speaker Change: We think there's a reasonable chance of hitting I E. Two pretty good chance of hitting 92.
Speaker Change: And a much better chance of hang on to it the point on one threshold in there was that I won with point over one.
Paul: Alright, Thank you Paul.
Speaker Change: Thanks.
Speaker Change: Okay.
Speaker Change: Our next question is from Joseph Schwartz with Leerink.
Speaker Change: Hey, Alan This is will on for Joe. Thanks for taking my question and congrats on the progress this quarter. So one for us on Angelman now with Korea Aso's.
Speaker Change: We're nearing sandoz development, including the one from Roche, who was recently revived are you thinking about the evolution of this market and do you see room for multiple treatment options and how do you think these assets.
Speaker Change: Further differentiate themselves and how do you think patients are going to be making decisions from a clinical trial or commercial therapy perspective. Thank you.
Speaker Change: Thank you well, we are not usually come reworking and competitive space with a lot of products in the same space. So this will be new thing usually we are working on first steroid treatments and our buy ourselves. So it's definitely a different space.
Speaker Change: I would say in regard to these <unk> ultimately the most potent and effective drug will be the one that will tend to dominate.
Speaker Change: But that doesn't mean, there might not be a place for other molecules in this space as well.
Speaker Change: I think they're very similar in terms of them being interests equally administered <unk>.
Speaker Change: But I do believe are driving is the most potent and has shown that and I think we've shown the best long term data continues improvement over long periods of time.
Speaker Change: There hasnt been shown for the <unk> molecule.
Speaker Change: The Roche molecule, that's sort of coming back into development.
Speaker Change: I am not concerned about I think.
Speaker Change: That drag is even less potent and has other questions Mark so.
Speaker Change: If theres more than one out there I think it will depend on efficacy and what people can show I do think that we have because we expanded our phase two study and we have almost 70 patients on drug. So we're going to have a pretty big body of kids have been on drug several years.
Speaker Change: I think how those kids are gonna doing are going to be even probably even more impactful than the phase III study that will be what people want to see what's my future like for my Kid defying on this and we know from them. Some of the early patients on there. The first one that actually had word Chad.
Speaker Change: Few words in the first year, but now she speaking few dozen words.
And has continued to gain ground over time, so I think that experience will be really important.
Speaker Change: I do think we are in the best position to be the leader in the ASO space and my hope going down the road that the top three <unk>.
Speaker Change: Treatments will be our first product than our second improvement and then the third nextgen that comes out.
Speaker Change: And because we intend to be the leaders in the instruments.
Speaker Change: Our next question is from Lisa <unk> with Evercore ISI.
Speaker Change: Hi, Thanks for taking my question I, just wanted to clarify sorry to ask so many questions.
Speaker Change: The map.
Speaker Change: Can you give us a little greater sense on where you are in terms of timing what happens from here could data and then I just wanted to understand follow up on an earlier question.
Speaker Change: If the data reads out positive <unk> positive and then take some time to analyze the data and come back to us with the data or is that is that all in one.
Speaker Change: In one press release.
Speaker Change: Yes, so on the timing of deal because I think people may some people <unk> had an unrealistic expectation that you would clean lock and analyze the data in a couple of weeks or something but.
Speaker Change: This is a fee international phase III study and this cleanup work is the entire data set not just the primary endpoint the whole thing because if it is positive.
Speaker Change: We need to go straight to preparing a BLA filing so.
Speaker Change: There is normally it takes a phase III around eight weeks of an international slightly to clean and lock the database plus there will be some time to analyze.
And have a DMC meeting.
Speaker Change: And disclosed at the time, we find the result, we will.
Speaker Change: Okay.
Speaker Change: We will sell.
Speaker Change: A much shorter time than we had before in terms of seeing what the data are we haven't yet precisely said, whether we will disclose it together at once or whether it would be.
Speaker Change: An initial read in some further so we're going to leave that open right now, but our expectation is that will be it will be sooner to getting the top line data than it would have been in I E. One where we had some other questions.
Speaker Change: So hopefully that gives you an idea of how it how it is going to flow.
Speaker Change: Okay.
Speaker Change: What so what I'll understand what took the IAA widen a little bit longer just to understand the difference with that that's my final question. Thank you, yes, what happened I want is that even if the interim was positive.
Speaker Change: <unk> wanted to have.
Speaker Change: The majority of patients have at least 12 months of data. So we would've had to keep running this study for a couple of months I mean other words, if I wanted to hit we say Oh, we're we're far enough along and so we would then continue collecting data for a couple of months to all children.
Speaker Change: More than half the patients had 12 months of data.
Speaker Change: And then we would have started to and we've been doing all the final visits and cleaning walking.
Speaker Change: At that time, so there had been a delay before we cleaned a lot. So you wouldn't be able to see the data for not just two months, but probably three to four months because we have to clean the market. So the timeframe here is much faster because we're going to clean lots of whole database. This time, and we would be able to release top line data sooner than we would have in Taiwan.
Speaker Change: Our next question is from Luca.
Speaker Change: With RBC capital.
Luca: Oh, great. Thanks, so much for taking my question Congrats on the progress maybe just one more on <unk> just to be Super Super clear in a scenario, where you actually don't hit at the second interim loss will the SMB share with you. The P value. Just wondering what are you will have a sense of whether you Miss by a net.
Luca: Aero margin or not and then maybe related is it fair to assume that the peer V for Oi as possible only if you hit that second interim look my understanding is that you need to get approved by the end of 2026 in order to get the priv given their sunsetting that program.
Luca: Any context there much appreciate it thanks so much.
Luca: Yes, so if we don't hit it well just find out that the study is continuing and we didn't hit it we will not get any key values, we won't know if its close.
Luca: We do have <unk> designation and we'd have to get approved by October so whatever timeframe, we file would have to be within the timeframe to get approval by October obviously by two it's easier. If we have to go to the end of the study then the time to file would have to be much shorter and the review rapid.
Luca: But I would also point out to you we do have breakthrough therapy designation for this program.
Luca: So I think there are reasons, why we could be able to accelerate things if need be but our goal would be to get this file in time to get a third CRB.
Luca: Short of that we certainly have already potentially <unk> in place at 111 gets approved.
Luca: Sanfilippo and if the <unk> 401 gets approved for <unk>. So I don't think theres anyone with potentially <unk>.
Luca: Still in play without the reauthorization I do believe the Bill will get reauthorized I think we've had assurances that is true, but I think right now there's some of the other matters that are top of mind in the Capitol Hill that that one will take a little while before that would come up.
Luca: And to clarify that.
The 140 <unk> in October of 2026.
Luca: We need approval by October 2026.
Speaker Change: Next question. Thanks, operator.
Speaker Change: Our next question is from Joon Lee with true Securities.
Speaker Change: Hello, Good afternoon, and thanks for taking our questions. This is Maggie on for June.
Speaker Change: I go on OIS and follow.
Speaker Change: Question on.
Speaker Change: Composition of ore types.
Speaker Change: So do you agree that sensors.
Speaker Change: MAA benefits of type one.
Speaker Change: Patients more than tied for entry.
Speaker Change: This is <unk>.
Speaker Change: The question.
Speaker Change: Well I know theres been some academic saying that but and I know some of them very good academics, but theyre actually incorrect because we already have data. So it's not it's a theory would be.
Speaker Change: Then in type one patients who are deficient in calls and we don't have abnormal costs and therefore, if we just make more bone it'll be okay, and the types of things as far as they have abnormal costs and therefore has not improved but that's not actually what we saw we.
Speaker Change: We see both of them have improved.
Speaker Change: Production of fractures.
Speaker Change: And in fact, the one fraction we did see were in type one patients I think where some of the ones <unk> types of use before so the truth is all of them are improved because.
Speaker Change: While one's a deficiency of college and one is abnormal collagen.
Speaker Change: Whether deficient or abnormal the net benefit of making more bone is bone greater bone strength and reduce fracture. So it actually works on all three.
Speaker Change: And historical clinical view of Oi is going to change because the truth is that even with abnormal collagen. The phones can be strengthened we believe in these patients and that's what we've seen and that's in the data from phase II and so we're confident that at.
Speaker Change: The type will not matter you get the same bundle density effect and the strength of improvement will be the same regardless of the college of mutation.
Speaker Change: Thank you very much.
Maury Raycroft: Our next question is from Maury Raycroft with Jefferies.
Maury Raycroft: Hi, Congrats on the progress and thanks for taking my question.
Maury Raycroft: I'll ask one on OIS, while just I guess based on what you know about the baseline characteristics in expectations for variation can you provide any perspective on how you're thinking about the range of effect sizes on <unk> reduction that would be needed to succeed on the second interim.
Maury Raycroft: Yes. So we've had that question various forms of it like what what's clinically meaningful fracture reduction I think were clinically meaningful most of you will say at least 30%, 40% would be clinically meaningful. This phosphates are probably <unk> or less so anything like 34% or better.
We don't have a sense now for sure what the.
Maury Raycroft: Power would tell us I was just as I said before.
Maury Raycroft: When the curves separate theyre almost linear essentially and so we saw them separate within two to three months of treatment, which means when they get to even just.
Maury Raycroft: <unk>, 10% improvement bone density there is already a separation in fracture frequency, but after that.
Maury Raycroft: It appears relatively linear which tells me then that the percent reduction on the Flubs won't really change that much over time.
Maury Raycroft: And therefore I don't think you can think about.
Maury Raycroft: Mike.
Maury Raycroft: When you hit will determine what percent reduction you get I think I think you have to think of it more as.
Maury Raycroft: A slope and the time as well.
Maury Raycroft: How far apart in two lines or how much how many fracs is accumulated in one arm versus the other to give you the power.
Maury Raycroft: Does that answer your question.
Maury Raycroft: Yes, yes, I think thats helpful. Thank you.
Laura Chico: Our next question is from Laura Chico with Wedbush.
Dylan: Hi, Thank you very much for taking the question. This is Dylan on for Laura Chico.
Dylan: FERC Davita could you extend further on key growth drivers in the quarter and maybe what is helping drive uptake more specifically and in Atlanta, a turnkey regions or I guess, what is unique about patient identification efforts in these regions.
Dylan: Okay.
Dylan: He has gone really well Latin America, but I think it's growing recognition of how much patients do but.
Dylan: I don't know Eric can be any thoughts on what you say about how why it's growing in Latin America, particularly well.
Dylan: As I have stated in the opening remarks.
Dylan: Net.
Dylan: Patients are having a good.
Dylan: Our experience with the product.
Dylan: And physicians are now treating more and more of their patients to include adult patients in the.
Dylan: Latam region as well.
Dylan: So it's a little bit about word of mouth and propagation of that through the pipe. We don't have a particularly prominent patient diagnosis function in Latin America, there are certain doctor I mean.
Dylan: Our employees are doing patient fine, but it's not quite the same because we don't have the same tools in South America that we have in the U S. Like we don't have the codes nine codes 10 codes and other things to help us but.
Dylan: Yes, so it's a little bit more word of mouth, but I think.
Speaker Change: It's impressive but I believe the sound.
Speaker Change: Feeling of doctors that this is transformative for patients it means they're just there.
They want to get more and more on when I went down to the meeting last year.
Speaker Change: Latin America Brazilian meeting on these patients.
Speaker Change: Clear difference from the very first meeting we did at launch.
Speaker Change: Every doctor had a story of how their kids were doing and were great.
Speaker Change: Grateful excited about it.
Speaker Change: We're happy to be able to do something for these kids. So I think that mood is going to is the fact, we're getting adults on is great too because we certainly have got more primarily peds on originally so yes. So in addition to the strong demand for both pediatric patients and adult patients.
Speaker Change: As I stated we have now have reimbursement with the national authorities in Brazil for sale as well as Mexico, Yes, that's what's really driven for Brazil, and Mexico, driven a lot of the increase in uptake rather than just named patient approach in Turkey is still under named patient, but the same thing is happening <unk> treating people to see what's happening.
Speaker Change: <unk>.
Speaker Change: And over a period of the year they see how their bones during other kids are doing.
Speaker Change: They get adamant about get more kids on and parents were friends of people find out and that's <unk>.
Speaker Change: Good drug will do.
Speaker Change: Even though our named patient setting.
Speaker Change: You'll hear about our story they all want to get something for their kids. So we're excited about that continued growth of the product internationally.
Speaker Change: I think the investment in Latin America, and the <unk>.
Speaker Change: <unk> care team and in Turkey have been.
Speaker Change: The word by being able to build a really solid growing business for the company and I think that is.
Sets us up well for when we bring citrus snap to the marketplace.
Speaker Change: Well, because I think theres lots of Oi everywhere as well.
Speaker Change: Thank you for your question.
Speaker Change: Our next question is from Jack Allen with Baird.
Jack Allen: Great. Thanks for taking the questions and congratulations on the progress made over the course of the quarter.
Speaker Change: One more of a logistical one on <unk>, Matt have you pointed investors towards how many of the patients had 12 months of data at that first interim readout. It sounds like the minority of patients, but I'd love to hear if you wanted to put a little bit more finer point on the percentage of patients.
Speaker Change: And then also on <unk>, Matt I wanted to ask you about any disclosures you made on the impact that such as <unk>.
Speaker Change: In pain, we recently did a call with a physician who mentioned bone pain as a key symptom for these patients and I'd love to hear any impacts such as an IPO.
Speaker Change: Thank you okay.
Speaker Change: I'll talk a little about the <unk> and then maybe you can touch on the peak.
Speaker Change: The impression scale scores or <unk>.
Speaker Change: It was a little bit about the pain I guess.
Speaker Change: So.
Speaker Change: Yeah.
Speaker Change: Just to understand the enrollment curve.
Speaker Change: We had a lot of the patients enrolled in the last two to three months of that trial is very much a hockey stick.
Speaker Change: So when we had the minimum was seven months at that time point, we had a lot of people who are at eight 910 months right and a relatively smaller number at the 12 two to 17 month timeframe relatively smaller tail alright. So.
The <unk> patients had less than a year at that time in order to get the majority to half a year you would take another two months or three months from the win the cut was made does that makes sense. So it's a very steep accumulation at the end a lot of the patients were.
Speaker Change: Less than a year then the majority of the lesson here at the first interim so it will be a significant difference in the number of patients that have.
Speaker Change: Let's say exposure beyond the two to three month period, where they get the bone effect. So let's talk about something other than practice and I think it's actually really important super proceeded to that things other than the bones, often our drivers let's start thought from what we've seen in the phase II data there, yes, no agree of pain is a big part.
Speaker Change: Part of the.
Speaker Change: And certainly very important to patients and an important part of the evaluation for the clinical trial and so we are focused on paying our comfort subscales and really focusing more on type of assessments that you would do with or physical functioning. We are also doing a traditional SF 36 public at best buy.
Speaker Change: It's definitely following panel very long term and phase III, we did hear a lot of improvement there anecdotal anecdotally, we have heard that patients have had a lot of improvement in pain scores.
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: Sure.
Yes, I would say to you based on how kids are feeling like Hey, I want to go to sports and stuff. They were feeling different too I mean, whether it's pain or fatigue or Gerry malaise. Please refer patients to offset pretty energized I think right and so.
Speaker Change: And so Thats also what happens preceded by the way for <unk> to pick up so fast because kids feel good parents see it and.
Speaker Change: I think that's happening with a Y too I think when your bones get stronger even a little bit stronger.
Speaker Change: Your body feels it you know it so we're excited about it.
Speaker Change: When we look at.
Speaker Change: How many patients we have for that program and the fact that it's more than even with XL age. It's pretty clear. This program should exceed what we've done with Chris feed and I think we will launch more rapidly. We just of course have to get our IAA too.
Speaker Change: Our final data in hand, and get to a file but we're excited about the opportunity being.
Speaker Change: The larger than it is even with Christina.
Speaker Change: But very few times, you get to do something amazing like that again and we're really.
Speaker Change: Thankful to have an opportunity to take on a bone disease like Austria osteogenesis imperfecta in turn turn it around for patients in the future.
Speaker Change: Thank you for the question.
Speaker Change: Thank you there are no further questions at this time I'd like to hand, the floor back over to Joshua young for any closing comments.
Speaker Change: Thank you. This concludes today's call. If there are additional questions. Please contact us by phone or at IR <unk> Dot com. Thank you for joining us.
Speaker Change: You may disconnect your lines at this time, thank you for your participation.