Ultragenyx Pharmaceutical Inc. Q4 FY2020 Earnings Call

Good afternoon, ladies and gentlemen, and welcome to the Fourth Quarter and Full Year 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. I would now like to turn the conference over to your host, Mr. Joshua Higa. Sir, you may begin.

Good afternoon, and welcome to the Ultragenyx Financial Results and Corporate Update Conference Call for the fourth quarter and full year 2020. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. I am Joshua Higa, Director of Investor Relations. And joining me on this call today are Emil Kakkis, Chief Executive Officer and President; Camille Bedrosian, Chief Medical Officer; Erik Harris, Chief Commercial Officer; and Mardi Dier, our Chief Financial Officer. I would like to remind investors that this call will include forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the types of statements identified as forward-looking in Quarterly Report on Form 10-Q that was filed on October 27, 2020, our Annual Report on Form 10-K that will be filed soon and our subsequent periodic reports filed with the SEC, which will all be available on our website in the Investors section. These forward-looking statements represent our views only as of the date of this call, and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statement. For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks related to our business, please see our periodic reports filed with the SEC. I'll now turn the call over to Emil.

Good afternoon, and thank you, everyone, for joining us today. 2020 was a transformative year for Ultragenyx as we executed on many of our strategic priorities. We now completed the fourth approval from our portfolio we had at IPO. And over the last couple of years have now refilled our portfolio with substantial opportunities in six clinical stage programs, four of which are entering pivotal studies. We also have 14 pre-clinical programs that are advancing our first mRNA program to the clinic this year. The efficient conversion of our pipeline to our next opportunities will allow us to accelerate our value creation and treat more rare disease patients with the first-ever specific treatment. From a commercial perspective, we achieved the upper end of Crysvita revenue guidance despite a global pandemic and received two US approvals and launched treatments for two more diseases with no other approved treatments.

Thank you, Emil, and good afternoon, everyone. I'm truly proud of how the commercial team executed in 2020 in the face of unprecedented challenges. 12 months ago, pre-COVID, we issued guidance for Crysvita revenue in our territories of $125 million to $140 million. Despite the stay-at-home orders, many doctors' offices temporarily closing to non-essential in-person visits and all the uncertainty of a global pandemic, we were able to finish the year at approximately $139 million, right at the top end of our guidance range. For 2021, we have issued guidance of $180 million to $190 million for Crysvita revenue in Ultragenyx territories. This represents between 30% and 37% year-over-year growth as we ended the fourth year of Crysvita's launch. This steady growth is enabled by many digital strategies to educate physicians in finding XLH patients and getting these patients on Crysvita, while ensuring that existing patients stay on Crysvita during this pandemic. We believe we will continue to see the mix of XLH patients on Crysvita shift towards a greater portion of adult patients. This will be driven by our increasing efforts on finding adult patients by expanding our outreach to more endocrinologists, nephrologists, and other specialties in the community setting. To support these efforts, we will expand both our commercial and medical field teams who will be focused on these harder-to-find adult XLH patients. In the middle of last year, we launched a TIO indication for Crysvita. The launch is going very well. We have converted the majority of clinical trial patients to reimbursed drug and are receiving Start Forms for TIO patients from the major metabolic bone centers. Reimbursement for TIO is progressing well and is consistent with XLH reimbursement at the same stage of launch. We will not be providing specific patient numbers for TIO, as sales in that indication are included in our overall Crysvita revenue guidance. Outside of the US, we are making steady progress in our discussions with health and reimbursement authorities. Demand remained strong across Latin America, as we continue to see more and more patients being granted injunctions required to gain access to named patient sales.

Thanks, Erik. Good afternoon, everyone, and thank you for joining today's call. We issued a press release earlier today that included a financial update, which I will briefly summarize. Company revenue for the year ending December 31, 2020, totaled $271 million. Crysvita revenue in Ultragenyx territories was $138.9 million, including $128.6 million from the North American profit share territory and net product sales of $10.4 million in other regions. Total royalty revenue related to the sale of Crysvita in the European territory was $14.5 million. Mepsevii revenue for 2020 was $15.3 million. We expect these revenues may increase modestly over time. Dojolvi revenue for the year was $13 million. This includes approximately five months of revenue following the US launch of Dojolvi toward the end of July and 12 months of named patient sales in other regions. 2020 total revenue also included $89.2 million of non-cash revenue related to the tech transfer services provided to Daiichi Sankyo as part of our strategic manufacturing partnership around the HeLa PCL and HEK293 technology. Our total operating expenses for the year were $601.1 million, which includes research and development expenses of $412.1 million and SG&A expenses of $182.9 million.

Thanks, Mardi, and good afternoon, everyone. On January 8, we issued a comprehensive press release that detailed the latest data, regulatory progress, and Phase 3 plans for our gene therapy programs. Therefore, today, I will briefly summarize our current status and next steps for our three pivotal stage gene therapy programs. DTX401 for glycogen storage disease, Type 1a, has completed the scientific advice process with the European Medicines Agency, or EMA, as well as held an end of Phase 2 meeting with the FDA. Out of these meetings, we have aligned on the Phase 3 study design and endpoints. We currently are on track to initiate this pivotal study in the first half of 2021. Shifting now to DTX301 for Ornithine transcarbamylase or OTC deficiency, we have received feedback from our initial scientific advice discussions with the EMA. And we'll have an end of Phase 2 meeting with the FDA, barring any unforeseen delays, by the end of this quarter. Based on the initial discussions, we feel confident about where we will end up with regard to the design and endpoints for this Phase 3 study. We currently are on track to initiate this study in the second half of 2021. Moving now to UX701 for Wilson disease, our third pivotal gene therapy program to enter the clinic in 2021. Earlier this year, we announced that the seamless, single protocol Phase 1/2/3 IND application has cleared FDA review.

Thanks, Camille, Mardi, and Erik. 2021 is going to be a full year with lots of important progress across our commercial and clinical programs. The active work in business development has refilled the pipeline with multiple late-stage catalysts with one of the best rare disease portfolios in the business. In the commercial portfolio, we're looking forward to continue expanding Crysvita in the adult market through greater efforts to find patients and outlying clinics and through pedigree analysis. We're also continuing to expand Crysvita use outside of the US, Latin America, Canada, and Turkey. Dojolvi is off to a strong start, and I know the team will continue to execute the launch for patients with LC-FAOD, who are in great and urgent need for a new treatment option. Our commercial Med Affairs teams have adapted very well to launching three products and four diseases in the COVID environment. Within our gene therapy business, we've broken ground on the manufacturing facility in Bedford, Massachusetts, for three programs going to late-stage clinical trials. We continue to advance our early-stage work in neuromuscular diseases of CDKL5 deficiency and Duchenne Muscular Dystrophy. We're also continuing to improve on the HeLa manufacturing technology with the new 3.0 system that will have even higher productivity and reduced costs of goods, making gene therapy a bio-modality for these larger higher dose indications on a global basis. Our nucleic acid therapeutics pipeline will also advance. We're making progress in resuming the SOP Phase 1/2 study in Angelman. We plan to initiate clinical enrollment for the mRNA UX053 and Glycogen Storage Disease type 3 or Debrancher deficiency. With our first mRNA program to come out of our collaboration with our partners, we also have rights for up to 12 mRNA and other nucleic acid therapy targets. The GSDIII program is also a great complement to our efforts in GSDIa and builds on our broader portfolio of therapies aimed at inborn errors of metabolism that have not been treated by more traditional means. The addition of setrusumab gives us a de-risked late-stage opportunity that will leverage our expertise in creating clinical pathways for rare genetic bone diseases. As you can see, we're at a great moment in our evolution as a company with multiple late-stage assets across therapeutic areas and modalities, all enabled by continued strong financial performance from our approved programs, strategic investing, and diligence. Now, let's move on to your questions. Operator, please provide the instructions for the Q&A portion of the call.

Thank you, sir. Your first question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Hello Maury. Are you there Maury? Well, that’s a very good question. We are doing great and thank you for asking. Maury, you may be on mute. Operator, why don’t we go on to the next caller until Maury gets his communications fixed.

Yes sir. Your next question comes from the line of Yaron Werber from Cowen. Your line is open.

Hey good afternoon. Thanks for taking my question. So, Emil, I got maybe the first question, the pipeline looks really good, right? I mean you've essentially got two drugs going into pivotal, another one potentially into a Phase II/III. I mean it's fairly full. Do you have more room for business development? Are you still looking? Or are you sort of good for the next year? And then, Mardi, I don't know if you can give us any sense. How do we model the Daiichi-related revenues? Do you have visibility that you could share with us? Thank you.

Great. Yaron, I think if you look at our portfolio, we tend to target having five to seven clinical stage programs. And right now, we would have six with what we're doing. So, we're in a relatively full state in terms of development stage programs. We are still continuing to look because we always continue to look. If there were something amazing, we wouldn't want to walk past it. We would look for that opportunity. But we potentially have the ability to leverage our commercial organization with a later stage opportunity. But I do believe from an earlier development stage opportunities, we're very full and we've been at loss and we've got a lot of work to do, and I'm excited about the portfolio. I don't think you can imagine being in a better place than what we've been able to put together over the last couple of years. So, Mardi, maybe you can answer the other question.

Yes. Real simply, Yaron with Daiichi, of course, the deal that we completed back in March was for $200 million upfront. From an accounting perspective, we have this non-cash revenue recognition that we believe is associated with the tech transfer of the deal. So, there's about $60 million plus left on that recognition of revenue and that should be completed in 2021. So that should be a pretty specific way to model it in 2021.

Great. Thank you.

Your next question comes from the line of Gena Wang from Barclays. Your line is open.

Thank you for taking my questions. I have two questions. One is regarding the Angelman syndrome. It seems that, if they already give you feedback, and Emil, just wondering if you can give a little bit more color regarding the amendment to the protocol. Is there any additional change versus your original submission regarding the protocol amendment? And my second question is regarding the dosing change. You used ddPCR for the GSD1 pivotal study and it changed the dose from 6e12 to 1e13. Just wondering, do you need to do similar change for the OTC program? And will you use ddPCR across all the future programs so that the dosing will be more accurate going forward?

Sure. Great. So, on the Angelman, we gave them this very large substantial amendment. They provided us a response with some specific questions, additional information, inquiries that they were interested in. Those questions did not change the plan we had proposed. We listened to what they put together and provided now an amendment to the protocol and provided all the things required in order to proceed ahead. So we'll wait and see their response to that. But the questions didn't really change our plan. They were basically in line. I think our plan is pretty well thought out. I don't think that there is much you could do to change it, but we'll wait and see for their feedback or maybe suggest ways to manage it. And they want to assure safety just like we do, and we're happy to work with them to get that done. But we feel comfortable, we're going to get back into treating these patients and the patients have been inquiring, and they really want to get back to treatment. So we're -- we want to get back to it. I think we're in good shape for that, and we’ll see what they say. On the GSD1 story, we're not really changing the dose. What we're doing is changing how we're measuring the dose. The total dose effect we're giving is the same as it was before. It's just what we're calling it has changed. The original PCR methods have some limitations and variability in them. They're not as good, and we've been working on the digital drop method, which is more reproducible, more validatable, therefore, a more accurate representation. It turned out for GSD1a is that we were really administering a vector quantity we considered 6e12 before was actually closer to 1e13 when you use a more accurate digital drop method. And it just relates to the techniques and biases of certain methods. For the OTC program, there is also a difference, and we are using the digital drop. However, it should be clear to everyone that the dose is the same, and what’s changed is the definition based on more accurate methods. This is important as we want to ensure the accuracy and the quality of the process, which gives confidence to both the FDA and ourselves on the amount of these particles we are administering.

Great. Thank you.

Your next question comes from the line of Cory Kasimov from JPMorgan. Your line is open.

Hey, good afternoon guys. Thanks for taking the questions. First one on Angelman, assuming you do, in fact, get that study up and running in the first half of the year as you're expecting. How quickly do you think you'll know whether the amended dosing and administration plan is working and avoiding the SAEs you saw originally? And then I have one follow-up on Wilsons.

Well, the way the protocol is proposed is that we will redose the existing patients, the five patients, and we'll also enroll another 12 patients in a staged manner and look at basically 4 doses, and then they’ll go into maintenance every 3 months. So by the time we get through 4 months of dosing with these patients, both the existing five and the additional 12, that will give us a sense of whether we are achieving the efficacy we thought after accumulating the effect over multiple doses at a lower level. We should expect to get that story later in the year, as it takes about 4 months for each patient enrolled to complete the dosing. If we can get through the monthly phase and show the substantial efficacy we observed before without the safety issues, that will help improve our confidence. Once they go on to maintenance where they're dosing every 3 months, we feel more secure that the safety will be better. The problem we encountered was only during the monthly phase. Therefore, if we can successfully navigate the monthly phase and achieve the efficacy we hope for, we’ll have a clearer picture by later this year.

Okay. That's very helpful. And then for your seamless Phase I/II/III for Wilson's, what's the process in terms of making go/no-go decisions here to move to the next stage in this particular design? Is it to be thought of as a truncated study across all three typical phases? Or is there something else that goes into it?

Well, there's 2 stages. In Stage 1, we're going to dose placebo and drug in three cohorts, a first dose cohort, 5e12, 1e13, and 2e13. So there will be a sequence of patients through three cohorts. During this period, there will be an interim blinded assessment to determine how the dosing is proceeding and what's happening. We will make a decision on dose following these three cohorts. At that point, we would know in a blinded fashion if we are seeing efficacy and if the safety profile is appropriate. We would expect to release some data indicating our progress, but we want to ensure we do not harm the conduct of the overall study while providing some insights. Is that helpful?

Yes, definitely. Thanks Emil. Appreciate it.

Your next question comes from the line of Joon Lee from Truist Securities. You may ask your question.

Hi, thanks for taking my question. So Emil, can you affirm that the FDA was generally in agreement that trendelenburg and lower dosing would be sufficient to avoid the SAEs? Or did they want something entirely different? And then secondly, what if any lessons are there from the failure of OV101 and Angelman? Is the placebo effect possibly an issue when using CTI IS? Just curious if there's anything that could be learned from that study to apply to your study? Thank you.

Sure. The FDA did not question trendelenburg and flush procedures because they have been widely used. We provided justification for this approach, as it has been done in chemotherapy for years, so it's not new. There wasn’t a question about that. It was more about understanding the events and our interpretations of what happened. They wanted more detailed information about MRIs and other findings so they could understand our perspective. Therefore, there was no question about the strategy on lower dosing. We feel pretty good about where we are at. We are making the right choices, and I think there's a good basis for our changes to be beneficial. Regarding OV101, I don’t think it has too much relevance for us as it would create more complexity if it were an approved product during our Phase 3. The magnitude of the effect we observed in our five patients was notably larger than what you might see from a placebo, and we have many other evaluations that supported our findings including sleep and mobility changes. We are confident this isn't simply a placebo effect; we have too much data supporting the efficacy.

And just quickly following up on the Angelman. You have not created a target for yourself. There are companies pursuing the exact same approach, start to stop. What kind of node do you have around your product that could protect -- keep your franchise well better?

Well, I think you've got to run fast to avoid becoming a target. That’s the truth. Our ability to execute is crucial. We are focusing on larger rare disease areas, and our strategy is not to go it alone. Our position with the Angelman program stems from the data produced by GeneTx and their significant findings, revealing their targeted knockdown is more effective than others. This provides us with a strong intellectual property basis and scientific insight improvement. The challenge faced by other methods attempting similar actions is significant as gene therapies must evenly deliver vectors across diverse neuron populations. Hence, this presents a greater hurdle than ASO methods, where we enable gene expression without forcing it, thereby harnessing endogenous regulation. This strong foundational basis gives confidence that engagement and control of more neurons can be achieved. Running fast while executing well is our credo.

Hi, Erik. Hi, Emil. Thank you for taking my question. So could you provide a bit of perspective on Ultragenyx strategy to differentiate cetuximab profile from burosumab given, as you know, both antibodies target Sclerostin? And in light of the fact that Amgen is also pursuing osteogenesis imperfecta with romo in a Phase I that was recently posted on clinical trials? And then secondarily, if you could comment on the advantages of targeting Sclerostin as opposed to RANKL or TGF-beta for osteogenesis imperfecta. Given as you know that Amgen is pursuing OI Phase III and OI with Prolia and Sanofi is pursuing OI with LENUMAB in Phase I. Thanks.

Thank you. This sounds like another variation of the target on our back question. We are very familiar with romo. In fact, Michael Minsky who works with us previously spent ten years at Amgen working on romo, so he has significant insight and knowledge. It's a good anti-Sclerostin antibody. Its main commercial potential has been around osteoporosis. They are running a study as part of their pediatric investigational plan for Europe. The important point is that they aren’t focusing on this population; the plan is required but not prioritized. Our approach for OI will allow us to adapt dosing uniquely based on the specific needs of this patient population, and we anticipate the dosing may need to be higher and to focus on chronic administration rather than just an induction phase. There is substantial potential benefiting from treating a larger patient pool within OI, and we believe we can maintain a competitive edge.

Thank you very much, and good afternoon. So just following up on the Crysvita co-promote. I know it's probably looking a bit ahead, but the co-promotion is set to change in 2023? And you just mentioned the mix between the pediatric and the adult patients. I'm just curious as we're entering the second part of this agreement. Is the focus on shifting towards adults a key driver to maximize the remaining trajectory? Or are there other strategic initiatives we should be considering? And then just one quick follow-up with regards to 810 in DMD. I guess following a competitor update from a gene therapy study, I'm wondering if you could opine a little bit on how you're thinking about alternative biomarkers in the DMD space? Thank you.

Thanks, Laura. With regard to Crysvita, we still have room to penetrate both the pediatric and the adult market. We haven't finished that process. We've reached a point where we have about 30% of pediatric patients on the drug. We're continuing our efforts to grow the pediatric market while also expanding into the adult sphere where the unmet need is larger right now. We are making significant investments to locate these patients. This isn't necessarily tied to the transition; it's simply about identifying opportunities. Erik, did you have anything else to add?

The only thing I would add is that it certainly is one of our top priorities in finding the adult patients. We've redirected resources to focus on that, both digitally and virtually. We also have plans to expand our commercial and medical field teams to target more physicians in the community setting where most of the adult patients are, to leverage this opportunity.

Moreover, each pediatric patient likely has three or four adults related to them on average, making it effective to use pedigree analysis in reaching out across regions. Recently, we've received more feedback from adults on treatment regarding their experiences; this increased recognition encourages more adults to seek treatment. Therefore, while we target both pediatric and adult populations, our focus will remain on optimizing growth in areas of substantial untapped need. After the transition, we will maintain our revenue as we will have a role in promoting medical genetics for the product in at least one segment of doctors.

Your next question comes from the line of Salveen Richter from Goldman Sachs. Your line is open.

Hello. Is that Salveen?

The question has been returned, sir. Your next question comes from the line of Liisa Bayko from Evercore ISI. Your line is open.

Hi, there. Thanks for taking the question. For DTX401 for GSDIa, are you going to be enrolling patients in Phase 3 from all the different types of mutation? Should we expect similar efficacy across those?

We are not restricting to a particular mutation. However, remember in GSDIa, about 80% of the patients are null, so it's likely the most homogeneous phenotype of null expression we can find. Thus, we feel quite confident that even if there are lesser mutations present, patients with less deficiency will likely respond similarly or better, based on our treatment of nulls.

Okay. Thanks.

Your next question comes from the line of Jeff Hung from Morgan Stanley. You may ask your question.

Thanks for taking the questions. For UX701, you went through the plans for the single-protocol Phase 1/2/3. So going forward, do you see this as the standard operating procedure for conducting studies for other gene therapies? Or was there something specific for this program that allows for the single-protocol study design?

There are some factors that make single-protocol design feasible. One of the key ones is confidence in the primary endpoint. In the Wilson case, with multiple approved products, we've established that urinary copper excretion can be the primary endpoint. Having a defined primary endpoint allows for straightforward design across the three phases. If endpoints haven't been defined, it becomes difficult to construct a single-protocol study. Does that make sense? With Duchenne, where knowledge of endpoints exists, a Phase 1/2/3 may be possible as those endpoints are already established. For CDKL5, because we are creating new endpoints, a continuous program might be harder to execute. Regardless, we can design studies either way. The key benefit of a single continuous protocol is the avoidance of lengthy regulatory query steps, saving about 8 months or potentially longer.

Great. And then for Crysvita, you talked about the focus on finding adult patients. But what's the current proportion of treated patients that are pediatric? I think in the past, you mentioned it's about 60%. Just curious if that's changed much over time? Thanks.

Yes. From new patient data, I don't know, Erik, do you want to add anything to this? However, it has been shifting more towards adult in terms of the fraction of current prescriptions.

The last time we reported on this, the mix was about 55% pediatric versus 45% adult. We've continued to see the overall shift toward a heavier balance of adult patients. In the last couple of quarters, we've been finding more adult patients than pediatric patients. We expect this shift to keep continuing.

Great. Thank you.

Your next question comes from the line of Laura Chico from Wedbush Securities. You may ask your question.

Thank you very much, and good afternoon. Following up on the Crysvita co-promote. The co-promotion is set to change in 2023? You just mentioned the mix between pediatric and adult patients. Is the focus on shifting towards adults a main theme to consider for maximizing the remaining trajectory? Are there other strategic initiatives we should be aware of? Lastly, regarding 810 in DMD, following a competitor update from a gene therapy study, I'm wondering if you could share your thoughts on alternative biomarkers in the DMD space? Thank you.

Yes, thank you, Laura. In terms of Crysvita, we still have room to penetrate both the pediatric and the adult market. We are not finished in that process. We currently have reached about 30% of the pediatric market. We'll continue to work towards growing both the pediatric and adult markets. That said, the adult market presents a larger unmet need, which is why we have been increasing our efforts there. This focus isn’t about the transition but instead around identifying opportunities. Erik, do you have anything else to add?

The only point I’d add is that identifying adult patients remains one of our top priorities. We have redirected resources to achieve this target through both digital and virtual strategies and expanded our field teams to effectively reach more physicians in the community setting where adult patients are typically found.

I also want to highlight that typically, for each pediatric patient on our drug, there are about three to four adults related to them on average. This allows us to use pedigree analysis effectively. We continue to receive feedback from the adult patients on treatment which enhances recognition and facilitates increased treatment adoption. Hence, while still focusing on pediatric patients, we see significant opportunities in the adult market. It’s all about optimizing the growth of the product. After transition, while the commercial role may be reduced, we will still play a role in promoting medical genetics for the product across certain segments of doctors.

Your last question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Hi, everyone. Thanks for taking my questions. I wanted to check in on Dojolvi; it seems like it's off to a really good start. I'm guessing you're not going to say too much more on traction with newborn patients and naive use. But can you provide specifics around progress in screening and getting uptake in these patients?

Yes. We haven't had much more to report in newborns; there are some newborns that have been prescribed. Additionally, we have had emergency cases that we have had to respond to quickly without the reimbursement process being a whole separate story. We’ve been managing those cases effectively. I don’t have any specific data regarding newborn uptake yet; we need to ensure that policies permit treatment for newborn patients. What I can say is that for patients we treat, reimbursement may come after; hence, we'll treat babies and work on reimbursement over time. However, in these urgent scenarios involving babies, we can't afford to delay. Therefore, we’re quite comfortable providing free medication quickly to patients and navigating the reimbursement process afterward. Erik, do you have anything else to add on the issue of newborns?

I would just note that our Ultragenyx hub has been very responsive to requests for newborn treatment, getting the product to these newborns in under 24 hours, even in emergencies as quickly as six hours.

That's helpful. Lastly, can you elaborate on UX053? What does the study look like going forward with enrolling types of patients? Can we expect to see data from it by the end of 2021?

Yes, we are expecting to have some data by the end of the year. Camille, could you briefly summarize the study?

Yes, thank you for the question, Emil. The study is primarily focused on safety, with the goal of identifying the dose and performing dose-ranging. We will have randomized cohorts of both placebo and drug patients. Initially, we’ll treat adults, then expand to pediatric patients.

Got it. Very good. Thank you for taking my questions.

Sure. Thank you.

And I am showing no further questions at this time. I would now like to turn the conference back to Mr. Joshua Higa.

Thank you. This concludes today's call. If there are additional questions, please contact us by phone or at ir@ultragenyx.com. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and have a wonderful day. You may all disconnect.