Q3 2024 Ultragenyx Pharmaceutical Inc Earnings Call
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Speaker Change: Good afternoon and welcome to the Ultra Genics third quarter, 2024 financial results conference call. At this time, all participants are in the Listen Only mode. At the end of the prepare remarks, you will have an opportunity to ask questions during the Q&A portion of the call.
It is now my pleasure to turn the call to Joshua Higa Vice President of an Investor Relations.
Joshua Higa: Thank you. We have issued a press release detailing our financial results, which you can find on our website at ultriganix.com
Joshua Higa: Joining me on this call, our Amel Kakkis, chief executive officer and president, Eric Harris, chief commercial officer, Howard Horn, chief financial officer, and Erik Crombez, chief medical officer.
Joshua Higa: 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 are actual results made differ material. Please refer to the risk factors discussed in our latest SEC 5. How now turn the call over to Amel.
Amel Kakkis: Thanks Josh and good afternoon everyone. This is a great time for all to genics as we successfully completed development work across our late stage programs and now our recent submission stage.
Amel Kakkis: If we achieve our poof, we'll tremendous authorities.
We expect to build further revenue momentum on top of our existing growing commercial portfolio.
Amel Kakkis: We continue to see substantial year-over-year revenue growth as we expand geographic access and further reach more patients with our medicines. This growth could further accelerate us up to three near-term BLA submissions and approvals for our treatment for both Sanflipo Syndrome Type A.
Amel Kakkis: and GST-1A and potentially for osteogenesis imperfecta.
Amel Kakkis: Thank you. Thank you. Thank you.
These three late-stage clinical programs could be first-ever approved treatments with the potential to dramatically improve the lives of patients and their families. Doing three submissions within the same year or so is a special opportunity we've earned with our investment and development in these last years, and we understand the importance of these efforts for the patient community.
Amel Kakkis: This quarter, we have continued to make progress across our clinical portfolio. I'll touch on a couple of points and leave the rest for Erik Crombez, our Chief Medical Officer, to discuss in his prepared remarks.
Joshua Higa: On UX111 for Sanfilippo syndrome, as we announced back in June, we reached agreement with the FDA that cerebrospinal fluid, heparan sulfate, could be used for the treatment of sanfilippo syndrome.
Joshua Higa: is a reasonable surrogate endpoint that could be used to support accelerated approval for the treatment of SAMHSA's Filippo syndrome. And we already have clinical data to support clinical efficacy of the product as well.
Joshua Higa: We have since participated in a pre-delay meeting with the agency where we aligned on the details of the VLA. We are on track to file around the end of this year. We greatly appreciate the FDA's flexibility and thoughtful approach to getting this product submitted and potentially available.
Joshua Higa: Last month, UX143, or citruzumab for oxygenus imperfecta, received breakthrough therapy designation from the FDA.
Joshua Higa: as a treatment to reduce the risk of fracture associated with OI type 1, 3, or 4 in patients two years of age or older. We're pleased that the FDA has recognized the potential for UX143 to offer substantial clinical benefit for these patients.
Joshua Higa: Before I hand it over to Erik Harris to talk about the commercial business, I wanted to acknowledge the work our teams have done around the world to bring these important medicines to patients. In Latin America, our team has already generated over $110 million in revenue this year with the bulk of it coming from Cretaceous, but also Mepsevi, Dojolvi, and Abkisim.
Joshua Higa: Across Europe and the Middle East, we are successfully navigating the country-by-country reimbursement process for IFKESA and MedSavvy. At the same time, we are continuing to address unmet need for CRISPR-Vita in Turkey and respond to growing demand for named patient access for Dozolbi.
Joshua Higa: In Japan, we launched FQs in the second quarter of this year in a recently reached agreement with the PMDA that Dojovi does qualify for a conditional filing package based on the current clinical data.
Joshua Higa: We expect to file the JNDA in mid-2025. These two products are key components in building our rare disease business in Japan and could ultimately contribute to the company's overall path to profitability.
Joshua Higa: Finally, in the U.S., we continue to support KKC's efforts commercializing CRISFIDA while also maintaining relationships with the healthcare providers treating patients with XLH and TIO.
Joshua Higa: We clearly have a firm foundation to build from as we think about a future launch of UX143 or Satsushimab in OI.
Joshua Higa: We're also calling on prescribers at the Centers of Inborn Errors and Metabolism who treat MEP-7 for MPS-7 and bilirubin for LC-FOD.
Joshua Higa: These are the same prescribers who could treat patients with UX111 for MPS3A, DTX401 for GSD1A, and our other gene therapies. The commercial leverage we are gaining in bone and inborn error products will be important contributors to our financial progress in the years ahead.
Speaker Change: And now I'll turn the call over to our Chief Commercial Officer, Erik Harris, to provide an update on the progress across our commercial portfolio.
Joshua Higa: http://www.youtube.com
Erik Harris: Thank you, Emil, and good afternoon, everyone.
Erik Harris: I'll start with Chris Vita where global revenue continues to grow impressively.
Joshua Higa: seven years into our commercialization efforts. In the United States, where our partner, Kiowa Caren, is leading commercialization, the demand for CRISPR-Vita continues to remain strong. Approximately 60% of the start forms in the quarter came from adult patients and were prescribed by community physicians.
Joshua Higa: across the U.S.
Joshua Higa: There are approximately 420 prescribers, with 40% or so writing more than one prescription.
Joshua Higa: This is encouraging, given adult penetration is in the low 20s, and suggests CRRSFIDA has meaningful room to continue growing. We are confident in our four-year U.S. revenue projections, given the strength of underlying demand.
Joshua Higa: Shifting to CRISPR-Vita in Latin America, where we lead commercialization, our LATAM team delivered another successful quarter by adding approximately 65 new patients to CRISPR-Vita, totaling now almost 700 patients on reimbursed therapy since launch.
Joshua Higa: Brazil is the largest market in Latin America and continues to drive the majority of the revenue in the region. We are, however, seeing increasing contributions from countries including Argentina, Colombia, and Mexico driven by increasing patient demand.
Joshua Higa: and many more. Thank you. Thank you.
Joshua Higa: As I mentioned on previous earnings calls, we expect quarter-to-quarter variability in LACAM revenue due to uneven ordering patterns, but remain confident in the underlying demand growth for our products.
Joshua Higa: Moving on to the Jovian.
Joshua Higa: Growth of new star forms in the third quarter continues to steadily increase.
Joshua Higa: In the U.S., we added more than 30 start forms and 30 patients on reimbursed therapy compared to last quarter.
Joshua Higa: resulting in approximately 550 reimbursed patients since launch. The split between pediatric and adult patients continues to be approximately 65% P's and 35% adults.
Joshua Higa: The number of new prescribers continued to grow, adding approximately 15 new prescribers in Q3 2024, with half of them writing more than one prescription.
Joshua Higa: and many more. Thank you. Thank you.
Joshua Higa: For Dujovi, across Europe and the MENA region, revenue is currently driven by named patient sales requests. They are over 230 patients treated under MPS across 12 countries in the region.
Joshua Higa: The majority of the demand is from France, but we are receiving an increasing number of requests from other countries within the EMEA region, including the Middle East.
Joshua Higa: I'll close with a few comments on FQSR where we have been launching this transformative therapy for patients outside of the U.S. with HOFH.
Joshua Higa: In our territories, the HOFH physician and patient communities continue to provide positive feedback on their experience with EFKISA.
Joshua Higa: The clinical data showing significant reductions in LDL levels on top of standard of care support the long-term potential for this therapy.
Speaker Change: Thank you for watching. Please subscribe. And as always, thanks for watching. And as always, thanks for watching.
Speaker Change: In the EMEA region, we have patients from all of the major countries, including France, Italy, Germany, Austria, and the Middle East, on therapy as a result of our commercialization efforts or responding to named patient requests as we navigate the country-by-country pricing negotiations.
Speaker Change: www.mytrendyphone.co.uk
Speaker Change: In Japan, the launch is continuing to build following the pricing and reimbursement approval that we received in the second quarter. As Emil mentioned in his opening remarks, Japan is expected to be an increasingly important contributor of revenue, not just for KISA, but for all of our programs going forward.
Speaker Change: With that, I'll turn the call to Howard to share more details on our financial results and for the quarter and guidance for the year.
Howard Horn: Thanks, Erik, and good afternoon, everyone. I'll start by briefly summarizing our financials that were reported in our press release earlier today.
Howard Horn: We reported $139 million in total revenue for the third quarter of 2024, which represents 42% growth versus the prior year quarter.
Howard Horn: Chris Vita contributed $98 million including $56 million from North America, $36 million from Latin America and Turkey, and $6 million from Europe.
Howard Horn: DiGiolvi contributed $21 million, Efkiza contributed $11 million, and Mepsevi contributed $10 million.
Howard Horn: Our total operating expenses in the third quarter were $271 million, which included R&D expenses of $170 million, SG&A expenses of $80 million, and cost of sales of $21 million.
Howard Horn: Operating expenses included non-cash, stock-based compensation of $42 million.
Howard Horn: In the third quarter, net loss was $134 million, or $1.40 per share.
Speaker Change: As of September 30, 2024, we had $825 million in cash, cash equivalents, and marketable securities.
Speaker Change: Net cash used in operations was 67 million for the third quarter and was 335 million for the nine months ended September 30, 2024.
Howard Horn: We expect 2024 net cash used in operations to be around $400 million for the year.
Howard Horn: Shifting to revenue guidance, we are reaffirming our total revenue range of between $530 and $550 million for the year that we announced last quarter.
Howard Horn: This reflects strong performance and trajectory across all of our products, including CRISPFIDA globally and the launch of Ivkiza in our territories.
Howard Horn: For CRISPR-Vita, we continue to expect revenue to be towards the upper end of our range of $375 to $400 million, which includes all regions and all forms of CRISPR-Vita revenue to Ultragenyx.
Howard Horn: Specifically, it includes CRISPR product revenue from Latin America and Turkey and cash and non-cash royalties from North America and Europe.
Howard Horn: We also continue to expect the Jolvi revenue to be between 75 and 80 million.
Howard Horn: With that, I'll turn the call to our Chief Medical Officer, Erik Crombez.
Erik Crombez: Thank You Howard and good afternoon everyone. In addition to the clinical pipeline progress that Emil has already commented on, we have also made meaningful advancement across our gene therapy programs.
Howard Horn: starting with DTX-401 for the treatment of glycogen storage disease type 1a.
Howard Horn: In our press release today, we shared new data from the crossover patients in our Phase 3 GlucoGene study. These are the patients originally randomized to the placebo group and who have now been treated with DTX401.
Howard Horn: 12 of these crossover patients have reached 30 weeks post-treatment with DTX-401 and demonstrate a clinically meaningful 62% mean reduction in daily corn starch requirement.
Howard Horn: This is double the reduction seen in the patients randomized to receive DTX-401 in the blinded part of the phase 3 study at the same earlier week 30 time point.
Howard Horn: Also, importantly, the patients originally treated with DTX-401 at the start of the phase three study continued to reduce cornstarch use while maintaining good glucose control through week 78.
Howard Horn: While the blinded design of the phase 3 study was important, we anticipated that physicians and patients would take a cautious and conservative approach with the reduction of quorum search without knowing to which arm patients were randomized.
Howard Horn: Now that all patients have received DTX-401 and unblinding is complete, physicians and patients are able to titrate quorum search with full, direct, and immediate visibility to all glucose values.
Howard Horn: which enables them to act more rapidly and appropriately, particularly to hyperglycemia.
Howard Horn: The cautiousness with cornstarch reduction in the blinded period reinforces the unmet need for these patients and the continued deep and ingrained fear for the consequences of hypoglycemia during times of fasting or increased metabolic demand.
Howard Horn: Shifting to UX 701 for the treatment of Wilson disease.
Howard Horn: Last month, we provided an update from the dose-finding stage of the Phase 1, 2, 3 study that included data showing that patients across the three dose cohorts demonstrated clinical activity as well as improvements in copper metabolism.
Howard Horn: In this initial stage, 15 patients were enrolled into three sequential dosing cords and followed for at least 24 weeks.
Howard Horn: We are seeing evidence of the establishment of the normal trafficking of copper with the loading of copper onto ceruloplasm for the safe transport of copper in the body and the pumping of excess copper into the biosystem for excretion from the body.
Howard Horn: As a next step, we plan to enroll an additional cohort.
Howard Horn: at a moderately increased dose and with an optimized immunomodulation regimen with the goal of allowing the majority of patients to discontinue current standard of care treatment before selecting a dose for the pivotal part of the Phase 1, 2, 3 study.
Speaker Change: I'll now turn the call back to Emil to provide some closing remarks.
Emil: Thank you, Erik.
Emil: Over the first four quarters of this year, we've continued to hit our marks by delivering growing revenue and advancing our clinical programs. I'll close quickly by summarizing our key clinical catalysts for the rest of the year.
Emil: For GTX-102 for Aynswern Syndrome, we are planning to share a program update at the upcoming FAST and Child Neurology Society meetings.
Howard Horn: This update will include data from patients in the Dose Escalation and Expansion Cohorts who have been on therapy for at least 338 days.
Howard Horn: The data will show that our Phase III study is very well-powered to succeed for the primary endpoint of Bayley Cognition raw scores and also for the key secondary endpoint of MDRI. We're also on track to initiate the Phase III by the end of the year.
Howard Horn: Based on our own clinical data and the novel science that supports it, we are confident that we are now the leader in this space.
Howard Horn: For the Phase III portion of UX143 Orbit Study at Sotusabab, there are two interim analyses planned, with the first anticipated by year-end or early 2025, and the second in mid-2025.
Howard Horn: In order to end the study early at the first interim, there will need to be an extreme and early separation of the two groups to meet a very stringent threshold of a p-value less than 0.001.
Howard Horn: In order to end the study early at the second interim, we'll spend a little alpha, and we have set the threshold of p-value to be less than 0.01.
Howard Horn: when there is a little more time for the groups to separate.
Howard Horn: In the event the data readout is not accelerated at the first or second analysis, the final analysis will occur in the fourth quarter of 2025 after all patients have been on therapy for 18 months.
Howard Horn: In the event an MR analysis clears our stringent threshold, we would only share that the threshold was met.
Howard Horn: Top-line clinical results would be announced several months later, as the study requires that the patient complete final visits over a couple of months and will need time to collect and prepare the data for a complete analysis.
Howard Horn: As I mentioned in the opening, we're also working on multiple BLA submissions, one for UX 111 around the end of the year, another for DTX 401 is expected in mid-2025.
Howard Horn: As we head into the final month of the year, I want to express my gratitude to the talented team at Ultrasonic for executing one of the largest late-stage pipelines in the industry. It is incredible to think that we could potentially launch three new therapies over the next couple years, bringing first-ever approved treatments to patients without any real options.
Howard Horn: With the approved programs we currently have, that would make 8 commercial programs in just over a decade on the public market.
Speaker Change: Thank you. At this time, we'll conduct our Q&A session, and if you'd like to ask a question, please press star one on your.
Howard Horn: and many more. Thank you. Thank you.
Howard Horn: and Jeff Higgins. Thank you. Thank you. Thank you. Thank you.
Howard Horn: for each time that you queue.
Speaker Change: You can press star 2 on your phone to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. And once again to ask a question, press star 1 on your telephone keypad and please limit yourselves to one question and one follow-up question.
Speaker Change: Our first question comes from Chris Raymond with Piper Sandler. Please state your question.
Chris Raymond: Hey, thanks, and congrats from us on all the progress. Maybe two questions. I guess first on the Wilson program.
Chris Raymond: Maybe Emil, what is, who is the ideal patient for this, for this gene therapy? Would this be, as you guys are envisioning, a commercial rollout suited for patients that are well controlled, maybe on copper chelators or zinc? Or would this be targeted, you know, only for those most severe patients?
Howard Horn: and then maybe also a follow-up on Satrusha Mab. Can you give a little bit more color on this negative binomial regression model that you're using? Just explain a little bit about what that means, what you're doing there. Thanks.
Speaker Change: Very good.
Speaker Change: Do you really want me to go into the math of that, Chris? All right, let's start with the Wilson question.
Speaker Change: We've talked about the Wilson program several times about who's the most addressable. There's about 20% of the patients are not really well controlled, can't tolerate the meds, are probably the highest most addressable population of 20,000 out of a population of 20% of a population of 50-60,000.
Howard Horn: http://TheBusinessProfessor.com
Howard Horn: Among the remaining, there are certainly a segment of patients that could do better than they are.
Howard Horn: but there may be some patients who are very stable and well controlled that may or not be most addressable. So we wouldn't necessarily assume that all Wilson patients are addressable, but we do think
Howard Horn: The combination of people not tolerating and those not getting optimal copper management are patients that more having clinical symptoms would be ones that might benefit from the treatment. And given how large the disease population is, that fraction of the total is still makes for a very large potential market.
Howard Horn: With regard to citruzumab, P.K. Tannen, our head of biometrics, a highly experienced biometric statistician who was at Genzyme for 20 years and has done probably more rare disease programs than anyone, believes the negative binomial model is the best way to do an event-driven analysis.
Howard Horn: And it's a basic model that the FDA has agreed to.
Howard Horn: be different between different patients.
Howard Horn: So, while I can't explain it, what I can say is the study is very well powered to succeed in the citruzumab orbit study.
Howard Horn: Thank you.
Speaker Change: Our next question comes from Tazeen Ahmad with Bank of America. Please state your question.
Tazeen Ahmad: Hi, good evening. Thanks for taking my question. On OI, Emil,
Tazeen Ahmad: Given the timelines that you've provided for the different interim reads,
Tazeen Ahmad: That's the first question. And then secondly, would the timeline to when this would become commercial vary significantly depending on...
Tazeen Ahmad: which at the time point the study would eventually stop, assuming that it would be successful at one of those stops, if that question is clear.
Speaker Change: No, I understand. So...
Speaker Change: Where the first term hits or not doesn't have any impact on the outcome. It has to do with how fast the line separates. Not whether they will separate or how powerful. In other words, it could be 0.002
Speaker Change: at the first interval and not hit, but be less than 0.01 at the second one just a few months later. But giving the hits a few more months of time for fractures to occur could help dramatically separate. So it doesn't really affect...
Speaker Change: And we think if we hit that level of threshold, it should be, but I don't think it speaks at all to the efficacy of the drug. It just speaks to the question of how fast they separate.
Speaker Change: There's a year difference potentially there.
Speaker Change: There is a substantial number of months between the first interim and the final. The second interim, the differential will not be as great because when the second interim occurs, everyone will have had a year. So that means we wouldn't have to wait further to collect any information.
Speaker Change: So the second one will probably not be
Speaker Change: as long after the interim. It'll be only a few months after in terms of BLA filing.
Speaker Change: So, you could argue why worry about so many, a few months here, a few months there.
Speaker Change: The value, the NPV value of the program was highly dependent on that.
Speaker Change: Each month represents a very substantial amount of value to the company, and as a company we...
Speaker Change: We look carefully at how time affects value, which is one of the most important parts.
Speaker Change: of How Do You Achieve Success in Rare Diseases is understanding the value story, not just cash spend in terms of execution. So a few months, by the way, has a very big impact on net peasant value, and that's why we press hard to get things done as promptly as we can.
Speaker Change: Thank you for watching!
Speaker Change: Thank you.
Speaker Change: Our next question comes from Anupam Rana with JP Morgan. Please state your question.
Speaker Change: Thanks for taking the question. This is actually Malcolm Kuno on Thron Pomp.
Malcolm Kuno: So what data should we focus on with regard to the near-term angel mint updates coming at the near-term medical conferences?
Speaker Change: Okay, well
Speaker Change: We'll provide a little bit more long term data on the group so it will allow you to see how the expansion
Speaker Change: Patients have been doing.
Speaker Change: going longer through day 338. The reason to focus on day 338 is that's the length of the phase three trial. So today we'll help give you a view of what it looks like at day 338 for that population.
Speaker Change: We're also going to show you the fact that it doesn't really matter if you use RAW or GSV. We're also going to show you the fact that it doesn't really matter if you use RAW or
Speaker Change: as your analysis of the transformation of one to the other.
Speaker Change: Not a problem. It doesn't affect the power. So we'll provide that information which was requested from a number of investors that we think will help settle people's questions about whether You we use the GSC or raw scores as we were planning based on the FDA's request
Speaker Change: So those are a couple things, and also we'll talk, we'll update on sort of overall safety in the Phase 3 plan going forward. So it won't be a massive update, but it'll be a nice step forward heading to Phase 3, which is where our minds are at, getting Phase 3 up, running, and completed.
Speaker Change: Great, thank you.
Speaker Change: Your next question comes from Gina Wang with Barclays. Please state your question.
Gina Wang: Thank you. Maybe just quickly follow the previous question. Will data at the FAST and the CNS meeting be the same data set? And I have one question regarding the CITRUSMAP Phase 3 study.
Gina Wang: The breakdown of the patient, specifically between age 5 to 12, 12 to 18, and 18 to 25.
Gina Wang: Great.
Speaker Change: That's quite a list, so thank you for the questions.
Speaker Change: So, the data cut for mangement for FAST and the PEDS child neurology meeting will be the same data set. There should not be differences between those two.
Speaker Change: We've gone to the first interim timing. The clarity on the timing is not based on data we are collecting, so it's not based on fractures.
Speaker Change: We said from the beginning it would be end of the year, early 2025, and then a few months later, we're being a little more specific, saying middle for 2025, but it was always a few months.
Speaker Change: So we weren't intending to change anything, those are just where the timeline is. What we did change a long time ago, we talked about having fractured number.
Speaker Change: But because it was so operationally challenged, we just estimated when we'd hit a certain number of fractures.
Speaker Change: None of the change in timing is related to fractures.
Speaker Change: We haven't put out baseline characteristics yet.
Speaker Change: have more type 3 and type 4 patients, closer to half or more, as opposed to what was in phase 2 where it was about a third.
Gina Wang: And so that's one difference. We'd expect those patients to have more fractures. We'd expect them, the case you tried to study, to have a higher fracture rate than what we saw before.
Gina Wang: But right now, we haven't put in the breakouts for age groups that are enrolled in the study either. It is spread across the age groups. It is primarily a PEDS study with a majority of patients in the PEDS age range. We are stratifying.
Speaker Change: in the randomization to make sure that we have similar populations in both groups.
Speaker Change: That's where we stand. Thanks for the good questions.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Salveen Richter with Goldman Sachs. Please state your question.
Gina Wang: Hi, this is Lydia Andre-Salvin. Thanks so much for taking our question and congrats on the progress. Just on Wilson's disease, when could we expect to see data from this additional Stage 1 cohort? And I guess, what would you want to see from this data set to gain confidence in the regulatory and commercial outlook? Thanks so much.
Speaker Change: Dr. Prasad Prasad Prasad Prasad Prasad Prasad
Speaker Change: Thank you for the question. So on the Wilson's fourth cohort, we're...
Speaker Change: Hoping to get that protocol in and get set up so we would start early in the year. It depends on how long it takes to global 5, but we expect that to be going on.
Speaker Change: Because we have to wait until those patients get at least 6 months, 30 weeks or so of treatment.
Speaker Change: It will take most of next year to get there, but we haven't yet put a specific timeline on when exactly the data will come. It will depend on how quickly we get the study accepted. We are doing it primarily in the US, that cohort, how fast it takes to get that settled and accepted.
Speaker Change: And then the fact that we have to enroll five and get all their data. So it's going to take a good part of next year.
Speaker Change: is, I would say, consistent reduction in standard care in the majority of patients, if not all. We want to see a majority of patients, because we believe to make a gene therapy viable, we want to see a potency that is distinct and profoundly important to patients.
Speaker Change: And while we have activity at this point, we think we need to see a higher fraction of patients off standard of care to make it worthwhile, and we didn't want to invest in phase three until we had that in hand, and so it makes sense to work at a higher dose. And mean modulation, we hope, will improve potency.
Speaker Change: as a simple way to improve potency. So that's what we're looking for. We want to see that we're really changing biology completely in a large fraction of patients.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: And our next question comes from Maury Raycroft with Jeffreys, please state your question.
Maury Raycroft: Hi, congrats on the progress and thanks for taking my question.
Maury Raycroft: For Sutruzumab, just wondering what are key learnings from the Phase 2, 14-month data update?
Maury Raycroft: at ASBMR that help you triangulate around fracture rates and chances of success for the first interim or second interim updates. And maybe just a quick follow-up, if you can clarify if you'll have new patients with less follow-up in the Angelman data updates that you have.
Maury Raycroft: and many more. Thank you. Thank you.
Speaker Change: Okay, so I think what we learned from the 14-month update on Citrusmab was in fact that
Maury Raycroft: These patients can have a very profound degree of separation and that
Maury Raycroft: that separation can lead to a majority of patients having no fractures over a significant period of time. The other thing we learned is that, particularly the younger patients have a dramatic improvement in vomital density. So I think what we learned is that how strong the effect could be.
Speaker Change: And that gave us more confidence in putting in the interims in the first place, because if they are separating very quickly, within two or three months, and if that effect size is large.
Speaker Change: that we had expected groups to separate early. We just don't know for sure. We set a stringent threshold for the first one, the second one less so, but that data gave us confidence that we can do that. It also gave us confidence we can lower the number of patients.
Speaker Change: Modestly, and shorten the timeline then to finish enrollment. So those are the things we learned and what we expect to know. And everything that we've seen so far tells us that we have a strong effect going on and we want to reach that as promptly as we can.
Speaker Change: With regard to Angeman, we are primarily focused on patients through day 338. We have patients at a whole series of different stages in the program. The main focus will be on people through day 338 at this point.
Speaker Change: Well, our minds are really focusing on setting up for phase 3 and the D338 data is really about...
Speaker Change: Telling people where we are on path for Phase 3 where a larger randomized study will become the most important piece of information we need to gain. So that's what the focus is, update what it would look like and help people see how the Phase 3 would set up based on our Phase 2 data.
Speaker Change: Thank you for watching!
Speaker Change: Got it. Thanks for taking my questions.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Our next question comes from June Lee with Truist Securities. Please state your question.
Speaker Change: Hi, good afternoon. This is Mehdi on for June and thanks for taking our question.
Speaker Change: So, on Angelman, could you please provide some comment on the Aurora study, given the patient's age from 2 to 64 and diverse mutation types that are included?
Speaker Change: So, what should be the optimal endpoint for a thesis study, and would Bayley-Ford cognition be the one for this study?
Speaker Change: Right, so you're talking about the Iona study, is that right?
Speaker Change: You know Emil, I think he's talking about the Aurora study, the open-label study that we had.
Speaker Change: Oh, I'm sorry. I didn't quite understand what he said. Aurora study. Yeah, so let's talk about the mean study ASPIRE. The mean study ASPIRE is 4 to 17 year olds with the deletion type, which represent 80% of the patients out there.
Speaker Change: For Aurora, this is a supportive labeling study. This study will take
Speaker Change: The younger patients who have a deletion, or older patients who have a deletion, to look at effect in those range. The idea would be to demonstrate an open label setting where they have similar safety and efficacy as we've seen in the deletion type that's within the randomized trial.
Speaker Change: like the ones that are in the deletion program, but have missense, EPD, ICD, the other genetic types of the instruments, so they will get a chance to get treated. The idea is to try to cover these various pockets of the population.
Speaker Change: on Genetics and Age.
Speaker Change: in the Aurora study. We believe one large randomized trial is enough to prove the cause and effect of the drug, and the Aurora study will help extend the safety and verify comparable efficacy in these other subpopulations.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Yaron Werver with TD Cowen. Please state your question.
Yaron Werver: Great. Thank you, Samuel. I got a couple of questions, maybe the first one just on Citrusomeb, and I totally understand that the need to
Yaron Werver: when you finish the study to have a couple of further assessments.
Yaron Werver: At the time in which, you know, this goes to a committee, an independent committee, and let's say based on the events, they decide to recommend to you to terminate the study.
Yaron Werver: I think they will do it based on the fracture rates and statistics and the hazard ratio. Can you at least let us know...
Yaron Werver: Hopefully when that hits and it becomes positive that you hit and the hazard ratio is X, Y, Z at a certain p-value.
Speaker Change: is the first question, or would you really just not say anything until later?
Speaker Change: And then secondly, just on 401, did you complete the tech transfer to your own facilities now that you have a filing around mid-next year, and anything you can share with us initially on margin and COGS, because you're going to be obviously scaling a whole new facility. Thank you.
Speaker Change: Thanks.
Speaker Change: At the time of the interim, we will not put out the hazard ratio or any other detail, partly because the study is not locked.
Speaker Change: All the database will not be locked. There's a certain part of it locked.
Speaker Change: And we have to collect a little bit more data in final visits. So with the database not locked, we don't want to put out any data of an incomplete dataset.
Speaker Change: So the interim will allow us to see that the primary endpoint is hit, but we'll want to lock the entire database before we, and we wouldn't want to endanger the study by releasing data from a database that's not fully locked.
Speaker Change: So that's why that will be a little bit delayed before we put out the data. The fact that it hits us should be enough to give investors confidence that the drug works in a big way and that we're on track to move ahead.
Speaker Change: Regarding the tech transfer, tech transfer has occurred. We are running PPQ lots in the plant.
Speaker Change: Our expectations of running them in the plant, we'll probably say, was around 40%. We haven't put out cogs or margins yet in the program, but by running it on our own plant, it does...
Speaker Change: substantially reduce our costs.
Speaker Change: We own the plant outright, and so our little cost structure to the plant will be an improvement over the contract manufacturer. But the ability to control and assure the...
Speaker Change: The contract manufacturer didn't develop the prosody.
Speaker Change: A lot of this is going to work way better. It's why we made the investment in the plan, because not only with 401, but the other programs in hand, we have the ability to leverage our cost structure and we'll help improve margin cost in gene therapy, which we think will be important for success to making a successful business out of gene therapy going forward.
Speaker Change: Thank you. Thank you. Thank you.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: And our next question comes from Yigan Lakomovitz with Citi. Please state your question.
Speaker Change: Thank you for watching!
Yigan Lakomovitz: Yeah, hi, thanks Emil and team. Maybe I missed it, but just with regard to DTX-401, it doesn't appear that you gave us the specific reduction for cornstarch
Yigan Lakomovitz: for the patients that were on the treatment in the 48-week primary period.
Yigan Lakomovitz: You have that information and just the way I'm thinking about it is I would think that they would catch up given there we know that they're there they received the gene therapy and should catch up to the The ones that were or the crossovers
Speaker Change: Yes, so the primary treatment group
Speaker Change: had a 41% reduction during the 48-week period in the during the blinded phase and what we said They're now they're getting better now. They are able to look at their glucose value so that they're going down getting better
Speaker Change: by 30 weeks hitting 62% versus what was about 31% at that point in time for the GTX-401 group.
Yigan Lakomovitz: So we're just saying we could double the reduction in corn starch by people knowing what they're on. The real reason for this, Higa, is that...
Yigan Lakomovitz: If they're blind to their glucose values, they don't know they're running high, and when they see a low, they didn't realize that an hour ago they were shooting sky high. So they have trouble reducing their starch when the only thing they can feel are lows.
Yigan Lakomovitz: The monitoring allows them to know when they are high and allows them to be smarter and more proactive. The thing that is important to understand also is that...
Yigan Lakomovitz: As the glucose, as the starch level doses come down and you lower your glucose, it actually will induce the transgene because lower insulin, higher glucagon will stimulate transgene expression.
Yigan Lakomovitz: It's almost like you need the transgene or the gene therapy to exercise, you need to exercise it a little bit. So it will become...
Speaker Change: synergistic effect of lowering cornstarch, driving glucose down, inducing more expression, allowing you to bring cornstarch down. So we'd expect the original treated patients to gain ground now and start coming down. But we think...
Yigan Lakomovitz: This explains a little bit
Yigan Lakomovitz: that the blinding makes it very hard for people to manage this disease without having...
Yigan Lakomovitz: direct and immediate knowledge of what's happening with their glucoses.
Yigan Lakomovitz: So we're just encouraged and we thought it would be important for investors to see that the effect is what we think it is and if you do it, apply it in the way it will be applied commercially, the patients can improve quite a lot in reducing the dependence on corn starch and particularly in their fear of dying suddenly by going too low in their glucose.
Speaker Change: Thanks. I guess what I was driving at is, will there become a point in time where you'll share the 78-week data from the ones that were originally on therapy from the very beginning in terms of the total cost?
Speaker Change: Sure, we'll put out updated data in a formal scientific meeting with all the data. If we'd like everyone to get through a particular point in time, we just thought we should put out this piece of data here. But we'll put out complete data on the 48-week group when they get to their...
Yigan Lakomovitz: second year through to show where they're at. But as we said, they're titrating further, so we feel comfortable that we're going the right way.
Speaker Change: and the past profitability I recall at the R&D day.
Speaker Change: Just over a year ago in New York, you had a sort of a qualitative slide on the path to profitability. It wasn't too specific as far as numbers and the exact year. So now that you're, you know, you're burning 400 million cash a year and have a little over 800 in the bank.
Speaker Change: I'm just wondering if you could comment any further on revised thoughts around the time to profitability. I know you've mentioned that the launch in Japan could accelerate that. Thanks.
Speaker Change: Yeah, well, the growing product portfolio, products approved and launches, including the new ones, will continue to help that. I'll let Howard go through it in a little more detail, but we're on the same path we've put forth before at the Analyst Day, and we feel good about
Speaker Change: The contributions of Akisa, for example, is starting to make.
Yigan Lakomovitz: The three other programs launching will help us. So maybe, Howard, you can talk about the path of probability.
Howard Horn: Glad to. Ugal, thanks for the question.
Howard Horn: What we have said is that with what we did in June
Howard Horn: and the monetization of PRVs coming from 111 and 143 that we feel like we have the cash or we will have the cash to fund our operating plan that gets us to a GAAP profitable quarter by the end of 2026. So that's the translation of what we said a year ago about that pathway.
Howard Horn: And then the underlying sort of logic of that is that we continue to see our commercial programs.
Howard Horn: grow in revenue. Add to that a little bit from launches but not an enormous amount. And then if you kind of level out on all the rest of the spending, that's how you get the P&L, the profitability, again by a quarter, about before the end of 26.
Speaker Change: Okay, thank you
Speaker Change: Yep.
Speaker Change: Our next question comes from Ed Arce with H.C. Wainwright. Please state your question.
Howard Horn: Hi, good afternoon, everyone. This is Thomas here asking a couple of questions for Ed. Thank you for taking our questions.
Howard Horn: So, first, a question for GKS102 for Ingenlund Syndrome, the Phase III-X5 study.
Howard Horn: So, we call this preliminary design that was discussed in April, and it incorporates a 12-week or 84-days primary efficacy timeframe period. Can you discuss the significance of this duration?
Howard Horn: And then the second question for 143, can you discuss development status, progress, what next steps that we can expect from this program in 2025?
Howard Horn: and many more. Thank you. Thank you.
Howard Horn: Okay.
Howard Horn: https://www.youtube.com.ac
Speaker Change: 143 and 2025 is all about the interims and getting to phase 3.
Speaker Change: We'll have the Orbit Study as well as the Cosmic Study that will be helped to go to file. And our expectation, depending on where we finish in the year, we take a few months after the data come out to finish the PLA and get it filed, but we expect to be filing sometime next year unless...
Howard Horn: We go to the final assessment, which will be at the end of the year. But it's really those two studies are the primary drivers. There will be some data from biopsies and a few other things that need to be done, but the package is really orbit and cosmic.
Howard Horn: Regarding DTX-102 and Aspire, I wasn't quite sure I heard the question. Maybe someone from Erik or others heard the question more clearly. Yeah, I think the question...
Speaker Change: Please see the complete disclaimer at https://sites.google.com or at https://sites.google.com
Speaker Change: Thank you. Thank you.
Howard Horn: Sorry, I think the question was on the importance or why we selected the follow-up period that we did.
Howard Horn: And I think, you know, obviously we want to give these children a chance to, you know, start to develop, gain new skills, and be able to detect that with the assessments we have there without, you know, letting the study go on too long. So based on the Phase 1-2 data that we've presented so far, we have a lot of confidence on not just the primary endpoint, but also key secondaries at that duration.
Howard Horn: Yeah, I think if we went shorter, like day 170, there were things that moved faster that you would see, but there's some things that took a little more time and you gain more separation, and that's why we felt it worth going to 48 weeks.
Howard Horn: Is that your question?
Howard Horn: and many more. Thank you. Thank you.
Speaker Change: Yes, that was it, just wanted to understand the duration of the data measurement so that helps. Thank you again for taking our questions.
Howard Horn: Okay.
Howard Horn: Thank you. Thank you. Thank you.
Speaker Change: Our next question comes from Jack Allen with Baird. Please state your question.
Jack Allen: All right, thanks so much for taking the questions and congratulations to the team on the progress made over the course of quarter I know there's been a lot of discussion on to choose MAB and the interim analyses on the call But I was hoping we could just step back
Howard Horn: and provide some more context around what triggers the interim analysis. I think there was a comment made by Emil previously about an estimation of time-to-fracture rates, and I just want to understand, are the interims set in stone internally as it relates to when those interims occur, or is there still incoming data that needs to be accrued to determine the timing of the interim analysis?
Speaker Change: Yes, so they're now set on a timeline, but originally our plan was to do the terms based on the events.
Howard Horn: It was operationally challenging to set up because it left a lot of unknowns to the team, so we decided just to estimate when we'd expect those fractures to be hit, the 60% and 80%.
Howard Horn: Lay those down on the timeline and just set that as fixed.
Howard Horn: We are confident that that is going to be fine because we're estimating based on the original fracture rate, but we believe the true fracture rate will be faster than what we saw from the historical fractures.
Howard Horn: at best,
Howard Horn: After the 60% would have been hit, for example, because of the fact that the fracture rate is probably faster than what we used to make the estimate.
Howard Horn: So it's just an operational choice, but they're set on the timeline now, which is the timeline we put forth in our current corporate presentation and what we just described. Is there any more color, Erik, on this?
Howard Horn: No, I think that's great.
Speaker Change: That's very helpful. Can I just ask one brief follow-up? I guess, how did you think about the potential time for onset of citrus in the map when you were making those fracture estimates? And I guess that's all I'm really interested in. Maybe when operationally did you make that change in the thinking?
Speaker Change: as it relates to estimating the fracture rate rather than going off the data.
Speaker Change: The time onset, the estimate we started gaining by looking at the 14-month data, it really looked by about three months or so in that
Speaker Change: the number of fractures had declined, and the number after three months, relatively few, and after six months, much, much less. And so our take was that, in fact, separation is probably happening within
Howard Horn: within three months. Now,
Howard Horn: For osteoporosis, people know that the separation occurs at around six months with an anti-sclerosin. So it's not so surprising when you go to children, it might be faster. But that's what we've learned now.
Speaker Change: Thank you for watching!
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Erik, did you have an answer for the second part of that?
Erik: Well, the second part, I guess, you know, when we decided to make these changes.
Erik: Yeah, I mean, it really was based on the results we started seeing in younger patients. When we originally designed this Remember Orbits of Phase 2-3, we really only had the original adult data set. So once we started seeing, you know, these really profound and much earlier effects in younger children, we really were able to recalculate power and the overall design of that Phase 3 part of that 2-3 study.
Speaker Change: I think he was thinking about when we decided to change from an actual event-driven interim versus a time-driven interim, is what you're asking.
Howard Horn: It was sometime during the year we made the operational decision to be easier just to do it right up front rather than wait and see. But I don't think it matters.
Howard Horn: Operator, I think we can move on to the next question. I think also underlying that is we're not looking at the blinded fracture rate so it's not that there was some sort of information that we had from the phase three that that caused that operational change.
Speaker Change: Our next question comes from Joe Shorts with Lyrinc Partners. Please state your question.
Joe Shorts: Great, thanks so much. I also have a couple questions on citrusamide. I was wondering first in ORBIT if you could talk a little bit more about how your...
Joe Shorts: Calculating the effect size and orbit, how that compares to how you did in phase 2, and then the range of effect size separations that might be needed in order to hit STAT-SIG at the different interim analyses would be very helpful, and then I have a follow-up on COSMIC.
Speaker Change: Well, we assumed a 50% reduction in fracture rates and a fracture rate of 0.7 for the powering estimate.
Joe Shorts: However, for the interim and the choice of doing interim...
Speaker Change: That was based on the concept that there could be more fractures.
Joe Shorts: events happening, not a higher fracture rate reduction.
Erik: And so, if there are more fractures, it improves the power to detect that result.
Erik: earlier, right, just because more events to find. So the effect size of 50% and the...
Erik: Fracture 8.7 was what was used to develop the power on the design.
Erik: Given that the fracture rate reduction...
Erik: was closer to 67 percent, which could be similar or higher with the binomial. I think we feel pretty comfortable that we're in good position in how we've designed the study.
Erik: So that's sort of what happened there with regard to the effect size.
Speaker Change: Okay, thanks. And then, what kind?
Speaker Change: Sorry, sorry, go ahead.
Speaker Change: No, go ahead. I'm ready.
Speaker Change: Okay, so in terms of cosmic, what kind of a treatment effect do you assume?
Speaker Change: In your powering relative to bisphosphonates, what do you hope to see for the citrus-meb arm? Are there any nuances in terms of how the endpoints in COSMIC are calculated versus orbit?
Speaker Change: Well, keep in mind something about orbit and the phase 2 part of orbit.
Erik: The vast majority of those patients have been on bisphosphonates, the bisphosphonates are in their bones. So when we're looking at the 67% reduction, that's really like...
Erik: The trees that I have on top of this last day, just to be clear, right, that's not...
Erik: So we'd expect that a similar differential would occur even head-to-head with bisphosphonates, right? It is really like an add-on, if you will, in orbit because they already have them in their bones. There might be some tailing off of the bisphosphate effect in orbit, but...
Erik: In COSMIC, everyone had to be on dysphosphonates up front. So our expectation is actually similar in terms of we went with the 50% reduction in fracture rate. Now, the fracture rate in little kids can be much higher, could be several-fold higher, which is partly why the study is.
Erik: in the 60 to 70 patient range rather than 150.
Erik: But that's our assumptions right now.
Erik: and many more. Thank you. Thank you.
Erik: Thanks again.
Speaker Change: Our next question comes from...
Speaker Change: From Jeffrey Hung with Morgan Stanley, please state your question.
Speaker Change: Hi, this is Michael Riadon for Jeff Hung. Thank you for taking our questions. For UX111 for San Felipe, given reductions in heparin sulfate and their association in Bayley,
Speaker Change: Is it safe to assume that HS is the sole biomarker data in the BLA, or do you expect to include other measurements like...
Speaker Change: Maybe more downstream markers like NFL, just in case.
Speaker Change: Thanks and have a solid.
Speaker Change: Yes, well, as we presented,
Speaker Change: We have Heparin sulfate. We also have ganglicides, which are elevated or probably pathologically important, which also decrease. And then we have NFL data, and we also have brain volume data. So we have a value chain all the way from the beginning through the biology that helps support what that efficacy is all the way to Bayley.
Speaker Change: Thank you, that's helpful. And then as a follow-up, for the Interim Statistical Map Analysis, like if you see a similar fracture rate like you would have seen in orbit, would that treatment effect have been like sufficient enough to like you know winding back to orbit? Would the like orbit have detected a clear enough separation at a like representative first interim analysis?
Speaker Change: Well, I think if the fracture rate of .7 and 50%, then the probability of hitting the first interim is much less.
Speaker Change: The first interim has a chance of hitting if the fracture rate is higher, and if the fracture rate reduction is greater, those would synergize and give us an opportunity to hit the first interim.
Speaker Change: Is that what you're asking?
Speaker Change: And that's very helpful. Thank you.
Speaker Change: Our next question comes from Kristen Kluska with Cantor Fitzgerald. Please state your question.
Kristen Kluska: Hi everyone, good afternoon. Thanks for taking my question. Satrusamab was hoping to get a little bit more color around thoughts about the placebo arm.
Speaker Change: We know that the five Bistoffinite studies had diverse readouts, so can you give us some context about
Speaker Change: how you developed that 20% figure.
Speaker Change: And then, is there any possibility in this trial that because patients are used to being quite inactive, that we could see more fractures on placebo if the protocol requires them to go to the clinic? Thank you.
Speaker Change: Yes, so...
Speaker Change: Now we're aware of five randomized studies to look at bisphosphonates.
Speaker Change: Three of them failed and two of them were successful.
Speaker Change: The two that were successful, there was an estimate that they had a reduction of 20% in fracture reduction. And they did make patients feel better, too, which is one of the reasons why people are using it less about fracture reduction than feeling better, which is probably dealing with, like, micro fractures or something of that kind.
Speaker Change: So the data are not really that compelling.
Speaker Change: But if you look at our own phase 2 data, the 67% reduction was on top of bisphosphonates, which were on the majority of those patients.
Speaker Change: It's pretty clear, but we should be able to see a substantial difference between the two. Now, if you talk about the placebo arm in the study,
Speaker Change: They're not getting the dysphocytes anymore during the study, so they will be weaning, which might have some impact on their
Speaker Change: over the period of the year. But in addition, most of them would be normally staying at home.
Speaker Change: And we know that by coming into the clinic alone, the incidence of accidents and fractures goes up. It's one of the reasons patients are elected to come in a placebo-controlled study. They know going back and forth to the clinic every month opens them up to having fractures. So we'd expect actually the clinical activity to actually increase their fractures.
Speaker Change: which would give us more opportunity to detect a difference between them. But because the data in the phase 2 were so strong,
Speaker Change: The doctors, the patient, decided they wanted to get in even if they got placebo because they realized they would cross over under drug before anyone else. They wanted that opportunity. So that's why we suddenly were able to get enrollment to crank up and go real well. People felt like this was going to be too big a difference to not want to be part of it.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Dagon Ha with Stiefel. Please state your question.
Dagon Ha: Hey, good afternoon, guys. Thanks for taking our questions. I wanted to, and we'll take a different angle to the Citrusmab line of questions that have dominated the call today. I wanted to ask about manufacturing for Citrusmab.
Speaker Change: Just, if you can maybe remind us, you know, what scale is it at? Does that plant actually have some precedent or regulatory success track record when it comes to getting a drug approved?
Speaker Change: And, similarly, when it comes to Buros Mabro-Crescida, it was, I guess, as of 2023 transitioned over as more of a royalty-based commercialization activity in the U.S.
Speaker Change: So just wondering, from a Salesforce standpoint, how ready are you if you were to hit the interim number one? Would there need to be a massive hiring spree that would need to get done? Thanks so much.
Speaker Change: Okay, so, on the manufacturing for the Truth-O-Map, it's the traditional stirred tank, you know, batch.
Speaker Change: type method.
Speaker Change: And it's currently at 3,000 liter scale. It is operating at a contract manufacturer in Germany that we use already for MEP SEVI, so they're already licensed and approved. So we're very comfortable on that.
Speaker Change: Given our view of the product and the size of the market, we'd expect to have to get another manufacturer in addition to that at some point, and we would obviously start working on that as soon as we knew we had our study.
Speaker Change: So, but we are well set up to launch and if the project is as well as we think it can, we'll need a second manufacturer to get going, but we're...
Speaker Change: We're confident in the manufacturer we have, we work with them, they are approved.
Speaker Change: With regard to the...
Speaker Change: situation in the US. While it has become royalty-based, we have actually had people in the field since the crossover in April 2023, and we currently still have 16 salespeople helping support our partner KKC.
Speaker Change: And we have some people within the org, within patient services and other places that have been moved around, filled other roles, that are still part of our team and have the knowledge and experience. So, there's a significant established base of people, but no doubt if we're launching,
Speaker Change: Given the value of the program and its potential, we would need to hire additional people, too, to launch that product. But I think at that point...
Speaker Change: I think it's going to be...
Speaker Change: real evidence that the value of the product will be high, that that investment will make a lot of sense. If we have enough established base, I think that'll allow us to be really efficient, effective, and really design a launch plan that will meet our needs. I don't know if you want to say anything else, Erik, about who we have and our expectations on launch.
Erik: I think you covered it, just about everything. The only thing I would add is that we still have our leadership team in place that successfully led the commercialization of CRISPR-Vita and had it on the right trajectory. So we will be ready.
Speaker Change: yeah that's our North American head or head of the patient services hub the team involved that the regional managers we've got a lot of great we got a great team set up so we'll be in good shape to take off
Speaker Change: Yep, yep, sounds good. Thanks very much guys.
Speaker Change: and many more. Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: And ladies and gentlemen, we've reached the end of the question and answer session. I'll now hand the floor back to Joshua Higa for closing remarks.
Speaker Change: Please see the complete disclaimer at https://sites.google.com or at https://sites.google.com
Joshua Higa: Thank you. Sorry we weren't able to get to all the follow-up questions. Feel free to reach out. I'd be more than happy to help facilitate responses. This concludes today's call. Thank you for joining us.
Joshua Higa: and many more. Thank you. Thank you.