Ladies and gentlemen, thank you for standing by. And welcome to the Ultragenyx First Quarter 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Please be advised that today's conference may be recorded. [Operator Instructions]I would now like to hand the call over to your speaker today, Ms. Danielle Keatley. Please go ahead.

Good afternoon. And welcome to the Ultragenyx Pharmaceutical financial results and corporate update conference call for the first quarter of 2020. We've issued a press release detailing our financial results, which you can find on our website at ultragenyx.com.I'm Danielle Keatley, Senior Director of Investor Relations. Joining me on this call are Emil Kakkis, Chief Executive Officer and President; Shalini Sharp, Chief Financial Officer; Camille Bedrosian, Chief Medical Officer; and Erik Harris, Chief Commercial Officer.I would like to remind investors 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 our 2019 annual report on Form 10-K that was filed on February 14, 2020, our quarterly report on Form 10-Q 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 relating to our business, see our periodic reports filed with the SEC.I'll now turn the call over to Emil.

Thank you, Danielle, and good afternoon, everyone, and thank you for joining us on today's call.Ultragenyx had a good first quarter despite everything going on. The impact of the COVID-19 pandemic has been felt by everyone at Ultragenyx, the patients we serve, their families and their health care providers. This is a truly unique point in the history of our society when everyone highly focused on their own health just taking precedence over virtually everything else.When facing this pandemic, the need for a robust and effective biopharma industry has never been more clear. The biopharma industry has mobilized its expertise to develop assays, drugs, and vaccines in dramatic ways, we are encouraged by the progress we are seeing.Although, Ultragenyx not directly working on a COVID vaccine, last year, we invested in and supported our mRNA therapeutic partner Arcturus Therapeutics who is developing an mRNA based vaccine for COVID. They recently announced potential important positive preclinical data for their mRNA COVID vaccine candidate showing that it is a potent at inducing a COVID-19 virus-neutralizing immune response at very low dose.The Arcturus mRNA vaccine forms unusual because it uses a self-replicating RNA technology that both amplifies [bioreactor] protein expression to induce an adaptive immune response and also stimulate inhaling immune system better. We look forward to data from their clinical study, which is expected to initiate this summer.For our own products in the pandemic, we are continuing to do whatever is needed to support our patients. We've worked to ensure our patient treat with Crysvita and Mepsevii, as well as those participating in our clinical studies continue to receive the treatments that they need during this challenging time.To-date only a relatively small fraction of our established commercial patients have had any issue with access. Fortunately, more than 8% of our Crysvita patients…

Thank you, Emil.During these extraordinary times, I'm extremely grateful for the relentless work the commercial and medical teams do every day on behalf of patients. The commercial team is especially focused on ensuring the continuity of patient care.Since launching Crysvita in April 2018, we have grown the patient base significantly and our top priority is to ensure that these patients continue receiving the important clinical benefits of this therapy.During this COVID-19 period of social distancing, we are seeing a small number of patients who are not able to go to their site of care for treatment. Our team is working hard to find alternative solutions for these patients, which includes home health services by a nurse.As Emil mentioned, we are aware of a handful of instances where a specialty pharmacy has worked with the payer to allow for self-administration. These are exceptions that have been initiated by the patient and their healthcare provider in response to a specific concern about COVID-19 exposure.In North America through the first part of this year, we have seen continued strong demand for Crysvita. More than 80% of patients received Crysvita through at-home nurse administration, which has helped to minimize any COVID related disruptions. As one would expect, social distancing will present some challenges for new patients to receive a diagnosis and start Crysvita therapy. We are being respectful and understanding of the additional burdens this pandemic has put on health care providers, which is required our team to come up with new and innovative ways to safely educate these providers on our products.Our field teams are conducting virtual speaker programs to educate a national audience of patients and caregivers. We are also hosting national webinars for health care providers that will be led by prominent KOL.Lastly, we have expanded our suite of digital tools…

Thank you, Erik, and good afternoon, everyone.Earlier today we issued a press release that included a financial update, which I will briefly summarize. Total revenue for the three months ending March 31, 2020, was $36.3 million. In the first quarter of 2020 total Crysvita revenue was $31.4 million. This includes $27.2 million in collaboration revenue in the North American profit share territory and net product sales and other regions of $1.6 million or a total of $28.8 million in Ultragenyx territories.Non-cash royalty revenue related to the sales of Crysvita in the European territory was $2.6 million. Recall that the rates of the royalties in this region were sold to Royalty Pharma in December of 2019. Mepsevii product revenue for the first quarter of 2020 was $3.4 million and UX007 named-patient revenue was $1.4 million.Our total operating expenses were $157 million for the first quarter of 2020. This includes $25 million, which was paid to GeneTx to maintain our option to acquire the company after their IND for GTX-102 was accepted by the US FDA. This also includes $20.2 million of non-cash stock-based compensation.Our R&D costs were $113 million. We expect our R&D cost to increase moderately over time as we continue advancing product candidates from early preclinical development into early and pivotal clinical study. Our SG&A costs in Q1 were $47.5 million. We expect SG&A to increase moderately over time as we support our commercial programs and potential new product launches.Our cost of sales was a negative $3.5 million for the first quarter of 2020, which includes a credit of $4.6 million that was agreed to during the quarter with one of our manufacturers due to previously produced inventory batches of Mepsevii that did not meet our quality standards. As a reminder, the company had previously recorded a reserve of…

Thank you, Shalini. I too wish everyone a good afternoon.I will discuss our progress with our two programs currently under regulatory review and we'll provide an update on the Angelman Syndrome program. Starting with UX007 for long chain fatty acids oxidation disorders or LC-FAOD, a devastating disease with significant morbidities despite newborn screening and current use of even chain MCT oil.The FDA is currently reviewing the new drug application and have set a PDUFA date of July 31, 2020. The review process continues on track and we expect to review decision by the PDUFA date. Importantly, all of the anticipated clinical and manufacturing inspections for UX007 have been successfully completed. At this point, we do not believe that any additional inspections would be required for completion of FDA's review.In addition to the progress in the US, our marketing authorization application is under review by regulatory authorities in Brazil and we continue discussions with regulatory authorities in the EU and Canada. Based on our experience, we know that many patients with LC-FAOD are not doing well on current management with even chain MCT oil and are seeking new treatment options. We have seen this interest through the significant number of requests for compassionate access and our named-patient program.Moving to Crysvita for tumor-induced osteomalacia or TIO, a rare debilitating disease for which approximately half of the patients have tumors that cannot be surgically removed leaving them with no other current treatment options. Erik previously discussed our commercial progress with Crysvita and I am encouraged that we are moving closer to a second potential approval for this medicine for the treatment of patients with TIO.This would be the first FDA approved treatment for patients with this devastating disease and the setting of an unresectable tumor. The review of our supplemental BLA is on…

Thank you, Camille.I will discuss our gene therapy programs and then we'll move up to your questions. Starting with DTX-301, our gene therapy for the treatment of ornithine transcarbamylase deficiency or OTC. OTC deficiency is an excellent urea cycle disorder that limits the body's ability to detoxify ammonia and urea and these patients can quickly deteriorate into full metabolic crisis, causing neurological deficits, hospitalizations, coma and in some cases death.At the beginning of this year, we reported positive data from dose cohort 3 and longer-term data from the first two cohorts of our OTC study. In cohort 3 we are seeing responses from all three patients and we believe this higher dose is achieved the consistent response and adequate level of therapeutic effects. In total up to six of the nine patients' study have responded and importantly three patients have come off their ammonia scavenger medications and liberalize their diet.We consider these patients complete responders and these patients appear to be metabolic cured. And next week's American Society of Gene and Cell Therapy Conference or ASGCT we will present updated data from the first three cohorts of this study and plan to hold an investor conference call after the ASGCT presentation to discuss both the OTC and GSD1a data update.For the OTC program, we planned to enroll the fourth cohort at the same dose as cohort 3, but using prophylactic steroid rather than reactive steroids to potentially enhance the level of expression, and provide more consistent expression. We've identified patients for this fourth cohort. Due to COVID-19 pandemic, we are waiting to dose these patients through the closure institutions, as well as the potential risk patient especially those using steroids.At this point, we still expect data from this cohort in the second half of 2020 barring significant further delays related…

[Operator Instructions] Our first question comes from Yaron Werber of Cowen. Your line is open.

So Emil, just a couple of questions on OTC and GSD1a in terms of - it sounds like we're going to get updates in a week from now at the conference. How - are we looking to basically reconfirm the prior data or are you thinking that is it can the data potentially get better? And then, secondly on GSD1a, you won't be able to have all the data, as you mentioned, obviously, patients can get hospitalized now for the glucose monitoring. So what data can we expect at that meeting and sure I might have a quick follow-up?

Sure, Yaron obviously, I'm not going to pre-run the actual data. So, what I'll tell you is that the OTC that we're expecting is from the cohort that you've already seen. So it will be more data from that cohort. So that will just be further data on the existing cohort that we announced on earlier in the year. The GSD1a the Cohort 3 is not been presented before, so that's new data and a new cohort done as the same dose as Cohort 2.But it will be a new three patients and they will have a significant amount of data, though not all the data points, because some of the later where we could not connect. But we think we have enough data to be able to present the story on Cohort 3 to the street. So that's what we're expecting. So, more of an extension for Cohort 2, but Cohort 3 should be some new data.

Okay. And then it sounds like you're going to be going to talk to FDA about the sort of the end of Phase II or the pre-Phase III meeting, at that point you probably will not have the fourth cohort of three patients and prophy steroids in OTC, and it looks like you're going to have more follow-up in GSD1a and hopefully by that point, you will get the glucose monitoring done as well. But I guess my questions are, as you sort of move into planning the Phase III, where in both programs you might still sort of enhance the dosing?Help us kind of think about, you don't want to hold the Phase III, but at the same time, you'll generate more data that can maybe even make the product even better suited for these patients. So, is the thought to move to Phase III and then potentially do a protocol change later on with the latest dosing or are you thinking about additional lines? Thank you.

Yes, I understand, thank you Yaron. We would go with the Phase III program we prefer and our expectation for OTC we will go with the prophylactic steroids arm I mean, design rather than reactive steroids. There has been enough data and enough programs to say that prophylactic steroids probably work better than reactive in general. We have enough safety information I'll suggest that.So our plan is to put forward the prophylactic steroids approach. We would like though to confirm that that works well by testing a few patients. But we can still begin the discussion with the regulatory authorities with the nine patient data we have in hand and the difference we're talking about it what I would call a drug administration related issue rather than design issue. The trial design, the randomized controlled design, the arm size, the size of the trial, the primary endpoint.All that can be talked through and work through, the only toggle is the prophylactic steroids and we think that the discussion we can have with the agency. So we will get in a prophylactic steroids, we've done before we actually start, but we can begin the process of regulatory conversation for OTC. For GSD1a, we are looking at these data.We will put it out and while we'll call after the data come out, so we can talk further about our next steps in the program. But in both cases, we're expectations ahead to the agency with the nine-patient cohort information to make our call on the design and conduct a Phase III.

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

My name is David. I'm - [indiscernible]. So my first question is on COVID-19. Do you see any incremental impact on the manufacturing specifically?

Yes, so far, we have not seen a challenge for manufacturing our supply chain appear to be intact. We also had substantial inventory on hand for all our products as we do for our rare disease program which gives us a lot of cushion. But at this time, we're not seeing any impact on the manufacturing for the three products that are necessary to their commercial and the third one would be the UX007 program. So far all is good and we're not having any issue with the supply chain.

The next question is on GSDIa, so I was wondering what are some initial thoughts on potential approval endpoints, so for example, potential hypoglycemia and those potential trial designs for Phase III?

I can start with the last part first, the trial design that we have been discussing both for OTC and GSD1a is a randomized controlled design and probably around the 40-patient total. That's our expectation. We have not gotten an agreement on that with the HCS the basic design. The primary endpoint of GSD1 still be discussed with the FDA, but we have several options ahead of us kind of hypoglycemia for certainly one of the original ideas that we would do and certainly is one that we can show and if that go on and it's important.We're also seeing that the reduction in cornstarch usage or requirement is another possible ability with continuous glucose monitoring opens up the door to looking at more of a real world setting, what is their hypoglycemia look like, or how good is their glucose control. The good part about GSD1 is that glucose control as well understood by the agency in the medical community. And so we can work through that story to develop a plan, not just primary.But secondary endpoints will characterize what we believe is an improved glucose metabolome situation where patients can reduce their cornstarch dramatically, achieve good control of the glucose and have other metabolic benefits. So we think there's a lot of ways to go, but whatever the endpoint will be, we'll talk a little more about it after we present our Cohort 3 data.

Our next question comes from Maury Raycroft at Jefferies. Your line is open.

I had GSD1a one as well, just wondering if - for the expansion cohort, if you can say generally if the modified time to hypoglycemia challenge and reduce cornstarch, if that's had an impact in this cohort?

Well, we have done it and we will see that data. But I don't want to discuss on it. I think it's pretty natural you've seen we gain less starch then get less glucose from it, that's right, pretty obvious. So we will be presenting that data shortly. But as you might expect, cornstarch quantity does impact how much glucose they get from it.

And then, for the continuous glucose monitoring I'm wondering if you were able to get data from the initial cohorts that could be compared with the expansion cohort and should we expect some sort of a dose-response comparison in that update.

We will be putting - getting glucose monitoring on the earlier patients but later in the course, we won’t be able to look at before and after very well. So that will be one limitation. But we can look and see how are they - what's a 24 hour fall look like, hypoglycemic events, how good is and the quality of their control, how stable is it in consistent compared to what we know is common for the - variability is common based on cornstarch treatment.So I think it will help confirm for us that the level of metabolic control glucose has improved in those patients, whether we can interpret the dose exactly. I think the dose determination would require more than just one test. I think we have to look at it from multiple parameters. There is only two doses that are in the program at this point 2e12 and 6e12.Our expectation is that we would assume that 6e12 is going to be a more potent dose based on the cohort data we have already. But between those two doses, I'm not sure CGM will provide the exact clarity. I think - but I do think it will be one of the components will help us confirm what we do going forward.

Our next question comes from Adam Walsh of Stifel. Your line of open.

This is [Edwin Zhang] on for Adam. A quick question on Crysvita for TIO, which I hope you will get the FDA approval very soon. First on tumors that of course TIO typically benign, is Crysvita mainly targeting those patients whose tumor cannot be surgically removed and how many TIO patients are in this category based on your estimates? Thanks.

Sure thank you. So, in general, the vast majority of the tumors are benign. There have been a few patients that had malignant tumors who do make FGF23 and do you have the bone problems associated. But the majority of patients we are talking about have benign small little tumors mesenchymal source tumors that are making a little bit of FGF23.We don't have good precise numbers on TIO in United States, but we had believed it's in the round 1,000 or 2,000 and around half of them have non-resectable tumors that would be more likely candidates for treatment. Non-resectable first means you have to have found the tumor, sometimes it's hard to do, and secondly, it has to be a tumor in a place that is that you can remove without causing other harm. And so there's a lot of ways you can end up in a situation where Crysvita might be a better option whether immediately or in the long run.So I would assume it's about half of the total population at this point in time. So relative to XLH it's much smaller but the population in TIO is very severe in many cases and very devastating and so there is a high urgency to treat, which is why we did a program before we getting compassionate use requests for access.

Our next question comes from Laura Chico of Wedbush. Your line is open.

I guess maybe a couple on the instrument program with GTX-102, I know you dose the first two patients already and just wondering if you could remind us, are there certain regions of the brain that are going to be more important to achieve distribution, I believe in the marine model we saw Ub3a expression pretty consistent across the entirety of the brain. But just interested in your thoughts there. And then related to that, what proportion of Angelman patients are currently on anti-epileptic drugs?

So with regard to the first part, I don't know that going into a very deep neural net discussion, probably on the conference call for work, but we can do a follow-up on that. I would say to you is the following, what we know from the data they have done in monkey, because you all need to tie DSOs getting to a wide variety of brain regions and inducing transcription of the Ub3a gene.So we know the treatment effect growth is broad throughout the brain regions and so we feel pretty comfortable whatever reasons need to get treated that there is regional distribution an uptake of the cell for it action and we can go deeper separately. But I'd rather not go into all that. The second part, you asked is a percent with seizures. I don't know if Camille have - to have that knowledge and I know it's significant fraction, but it's certainly not all of them. I don't remember the number off on top of my head, this is substantial fraction. Camille, any thoughts?

Yes. Thank you, Emil. Thank you for the question. Exact proportion, I don't know either, but what I do know is that most if not all patients do have an abnormal EEG, which is quite pathognomonic of the disorder.

Our next question comes from Yigal Nochomovitz of Citi. Your line is open.

This is Samantha on for Yigal. Thanks very much for taking the questions. On the Daiichi manufacturing deal, it's so interesting and in particular it's non-exclusive, I wonder can you first speak specifically what makes the manufacturing platform unique in terms of scalability versus others in the space. And also can we expect you to be interested in doing similar deals with other companies in the future?

Well, I can answer the second part first, which is, yes, we are interested in doing other deals. We wouldn't do many because we do have to do tech transfer support the partner with Daiichi, but we could do another deal or another two. The basic thing that's important that they're buying into is the fundamental reality is that it's very hard to do triple transaction in very large scale. You can get 200, 400, 500 liters getting to the 1000, 2000 will be quite difficult to do reliably and to mix and create besides the fact that the plasma dose is not scaling it is essentially linear at scaling which means cost don't continue to go up.So the HeLa system is the reliable 2000-liter culture system and because HeLa cells are very strong growers and they are growing suspension, we can basically take a clonal cell line which has the information to guide the production of AAV and grow into 2000-liter fully healthy fast-growing culture and then just add adenovirus small amounts, so it is a very efficient infect the entire culture, just like you would if you're doing vaccine manufacturing and this create trends the whole tank into an AAV production machine the cells start growing start making AAV.So the idea is we can grow the cells to large scale in a very healthy situation and then, in fact, the more efficiently, just going to be way more efficient than doing triple transaction at large scale. And we are talking about 2000-liter scale, which is the largest main scale it's out there that's because that's disposable reactor side, we believe the HeLa system could potentially use for 10,000-liter if we create the right stable colon and so you could even go larger, but it wouldn't be a [indiscernible]…

Thank you very much for all of the detail. And just on the tech transfer, can you speak about the typical timeline for completing that is?

Well, it's over an 18-month period expected, although there is a period of continued support for a five-year period, but most of the tech transfer expected over about an 18-month period and basically their people come to us, we will go to Japan, and of course, once we're all moving around. The idea is to teach them how to do all of it and to help them create their own PCL lines and do their own manufacturing in Japan. They have a plant that they're going to convert to that use.

And just one more if I could. With the prophylactic steroids cohort currently paused before you can dose the patients wind up, assuming this headwind continues a bit further into the second half. How many weeks on therapy will you need before you're confident that you can advance into the Phase III while using the prophylactic steroid dosing method?

Well, we will be advancing the Phase III plan in parallel with doing this. So this will allow us to kind of being able to before we do first patient in, we will have a significant data. Obviously, we think probably gives enough to say whether patients are doing well but it's more like 24 weeks to know how well UHS is and they've got enough steroids, but so, that's a kind of timeframe. But what I'm saying to you is we can keep working the plan for Phase II up until the first patient in.What I said our plan would be to go with prophylactic steroids is our proposal and just getting that confirmation there is nothing unusual happening to be able to reassure FDA that – this is and ourselves that there is no issue with doing it that way. As long as the first 12 weeks go well, we know it's safe, we know what the potency looks like in that timeframe and we will collect data probably from 24 weeks to get a sense whether we're getting better potency at least.

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

This is Turner on for Cory. Just on the Angelman study. I'm curious how frequently you are assessing functional endpoints and what's your confidence to be able to demonstrate an improvement in the 128-day timeframe. And just to that point, what the physicians are working with or interactive with, what do they deem as meaningful improvements from baseline of those functional endpoints? Thanks.

Very good, that's a very long detailed question. But I will – the Angelman program should be up on clinical trials, but I'll have Camille answer your question on the frequency in general, certainly at a high level. I don't know if we will answer all the changes in every endpoint at this point, but Camille go ahead.

Right sure, thank you. And well, thank you for the question also. Yes patients are evaluated to every month as well and there are a large number of assessments across a number of domains because these patients experience developmental and debilitating abnormalities along the way. So there are a number of assessments. In terms of what is meaningful for the patients as you can imagine sleep dysfunction, they balance abnormalities difficulty walking that leads to falling, seizures as was discussed previously, and most profoundly the inability to speak and varying degrees of not being able to communicate as well.So right now, we're learning in this first in human study and as we go forward, we'll be able to described and discuss the abnormality in this study, but also what we're seeing in terms of what is meaningful.

I would add, as we get further along in the program closer to actually having data, we will provide more depth to the endpoints and expectations of what meaningful. All the endpoint do have meaningful threshold through what mean but how precise that is, you are talking about multi-system disorder like this, it's complex. So we need to still learn, as Camille has noted and we look forward to providing more detail about the analysis and the interpretation that data as we get closer to it. Thank you.

Our next question comes from Liisa Bayko of JMP Securities. Your line is open.

This is Jon Wolleben on for Liisa. Thanks for taking the question. Just on the 007 launch. You mentioned that there are about 160 metabolic centers that you're looking at. Can you discuss kind of your launch strategy and how you're hearing those potentially or what doctors you're targeting at first and how that might change over time?

Sure, I'll start and let then Erik finish. We are very familiar with the 160 metabolic centers. We are already seeing them for MPS. We're seeing them for our OTC program, GSD1a program, GSD3 program. I've seen them for Cuzan, [Proterazyme], for Naglazyme. So it's a group that we've seen a lot of triple product very well. We know these centers we’ve been involved in a number of clinical trials with them, but simply there are with key simulators. But there will be a segment among of those and but maybe I'll let Erik talk about the strategy we are using to launch [indiscernible] metabolic center.

Yes thanks, Emil. As we stated, the majority of the patients are at those 160 metabolic centers across the country and where we already have a strong presence and strong relationships. And then there is also high awareness at those centers around 007. So, our primary focus at launch is going to be transitioning those trial patients onto commercial therapy, and we expect those trails to also prescribe 007 for some of the other patients that didn't end up in the trial.So we think we'll be able to leverage our current infrastructure with the small – relatively small and efficient team to support the launch somewhere between five to 10 incremental hires.

Thank you. Our next question comes from Vincent Chen of Bernstein. Your line is open.

This is Brian on for Vincent. I guess one on the Wilson disease program. I was wondering if you could provide any color just on how you're thinking about what patients you might be going after. It's just, my understanding that largely speaking Wilson disease is pretty well controlled by Chelation therapy and this is also a very large indication. So I guess I'm just wondering how you're thinking about a target patient population there?

Yes thank you. There will be some Wilson clinical data at ASGTC on the programs that you reference in Wilson we submit for that data coming out there. The clinical strategy right now if you look at patients that clearly have a significant, they are still on their drug. We clearly have significant symptoms. It is very, right now at early stage we want patients who are not acutely ill because we need to establish the safety and the design the study will have patient first being studied that are relatively stable and then the patient population will expand later.We haven't really put out those details yet because we haven't discussed in with regulatory authorities. But clearly, when you look at the 50,000 plus Wilson patients there are some may be doing quite well on their key leaders and may not need additional call but the focus for gene therapy is on a substantial fraction that are still having progression of disease or still having symptoms despite Chelation.So I think there is a significant fraction of patients in there and ultimately the program will focus on those.

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Danielle Keatley for any closing remarks.

Thank you and this concludes our call for today. A replay will be available soon and if you have additional questions, please contact us by phone or at ir@ultragenyx.com. Thank you for joining us.

Thank you. Ladies and gentlemen, this concludes today's conference. Thank you for participating. You may all disconnect.