Ultragenyx Pharmaceutical Inc. (RARE) Q4 2016 Earnings Report, Transcript and Summary

Good day ladies and gentlemen and thank you for standing by. Welcome to the Ultragenyx Fourth Quarter and Full Year 2016 Financial Results and Corporate Update. At this time, all participants are in a listen-only mode to prevent background noise. [Operator Instructions] Now I would like to welcome and turn the call to the Vice President of Strategy and IR, Mr. Ryan Martins.

Thank you, good afternoon and welcome to the Ultragenyx Pharmaceutical Financial Results and Corporate Update Conference Call for the fourth quarter and full year of 2016. We have issued a press release detailing our financial results which you can find on our website at Ultragenyx.com. I am Ryan Martins, Vice President of Strategy and IR. With me today are Emil Kakkis, Chief Executive Officer and President and Shalini Sharp, our Chief Financial Officer. I would like to remind investors that this presentation contains 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 events or statements identified as forward-looking in our quarterly report on Form 10-Q filed on November 8, 2016, annual report on Form 10-K for the year ended December 321, 2016 that will be filed soon and our subsequent periodic reports filed with the SEC which will all be available on our website at Ultragenyx.com in the Investor 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 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.

Good afternoon, everyone and thank you for joining us. I'll start by discussing our recent progress and milestones and Shalini will then give you an overview of our fourth quarter and full year financials. This past year we advanced each one of our clinical development programs. And if you look back at tour pipeline when we went published three years ago, you'll see that all four product and five indications that were in development at that time have moved forward. Over the past we advanced the products from Phase 2 studies into the pivotal Phase 3 studies are on to the regulatory filing phase. As we further progressed to late stage development and near commercialization, we were also actively building our early stage pipeline. In 2016, our translational research program grew to two new partnerships with Takeda and St. Louis University and today we have now total of seven early stage programs that we expect will help replenish our pipeline over the next few years. We generally do not disclose the disease targets in early stage programs until we are confident we are moving forward with the clinical program, both for investors, but also for patients. We don't want to inappropriately raise our hopes until we're really sure we have something. We finished 2016 with positive data from our Phase 2 study of UX007 in Long-Chain Fatty Acid Oxidation Disorders. We showed a significant reduction both the frequency and duration of major clinical events, including hospitalizations. We are impressed with result because getting a statistic significant reduction in major medical events in the study of only 29 patients is hard to do. The overall data, as well the pattern of production with specific subtypes of rhabdomyolysis, cardiomyopathy, hypoglycemia events corroborated our previous data from the retrospective compassionate use study that we conducted and published. Based on these data we are further developing the Phase 3 design and endpoints before meeting with regulators and initiating the study in 2017. We are now considering an event-based study, given the strong clinical meaning and value provided by that type of data. For KRN23, in December of last year we filed our marketing authorization application for the treatment of XLH in Europe. The filing was validated by the European Medicines Agency and at the end of the year we had - we expect to have an opinion from the committee for medicinal products for human use by the end of 2017. I'll now go through our upcoming milestone for each program starting with KRN23. In the first half year we expect data from the Phase 3 study of KRN23 in 134 adult with XLH. The study compares KRN23 to placebo over 24 week period and evaluate change in serum phosphate levels as the primary endpoint. In discussion with FDA they have indicated, they will require achieving a statistic significant clinical improvement in addition to an improvement in serum phosphorus, which included pain alone by the BPI question number three for the clinical valuation, but after evaluating our burden illness date in 165 HLH adults, in our recent 24 and 48 week Phase 2 data in 20 adult, we believe that both stiffness and physical functions are also substantial disease manifestations for XLH in addition to pain. We also observed that all three measures appeared to respond to KRN23 treatment. In the meantime we've now also validate the WOMAC evaluation of both stiffness and physical function in XLH patients which support their use of key secondary endpoints. As a result of all clinical data and validation work, our adult Phase 3 will include all three measures pain, stiffness and physical function as key secondary end point, all three will be evaluated just in for multiplicity and we believe that all three these endpoints are clinically meaningful to this patient population. And the positively better support the values used in KRN23 adults and just pain scores alone. We expect to file our Biologics license application with KRN23 in second half of 2017. Based on the full 64 week data from our pediatric Phase 2 study in the adult Phase 3 data, a positive. We'll be discussing detail's mission in a prevailing meeting with the FDA. Moving on to rhGUS, following discussion with FDA and EMA last fall, we are preparing a regulatory filings in the US and Europe and plan to submit them in the first half of 2017. For UX007, we plan to initiate a randomized, placebo-controlled Phase 3 study in approximately 40 patients with the movement disorder phenotype of Glut1 DS and we expect that study to start imminently. In the study disabling movement first will be recorded by a patient diary. For the Phase 2 seizure study the last patient visit occurred in the quarter 2016 and we expect to announce data from the study in the first quarter of the year. Placebo-controlled control 3 to 1 randomized study enrolled 36 patients with either observable or absence seizures - observable seizure captured on a daily basis through patient diary maintained by the patient or caregiver and absence seizure measured through overnight EEGs. The primary endpoint will look at the reduction, the frequency of seizures of either observable or absence type over the week treatment period compared to the run-in period and compared to seizure reduction rate in the treatment arms to the placebo arm. As a secondary analysis of the prime member we will look at the reduction of each type of seizure, absence or observable separately within that treated group from baseline. Secondary endpoints include a responder analysis looking at the percentage of patients who have greater than 20% reduction in seizures. We don't have an overall target for the mean reduction study, but on individual basis, I fisher in the reduction in seizure frequency is accepted in the US clinically meaningful for a patient. Lastly for ACR, we think data from the pivotal Phase 3 study in GNE myopathy in the second half of this year. The double blind placebo controlled international study evaluates the efficacy and safety of Ace-ER compared with placebo over 48 weeks in 89 patients. If these data are positive we plan to submit an NDA and a MAA. I'll now turn the call over Shalini to provide an overview of our financial results.

Thank you, Emil. And good afternoon, everyone. We issued a press release earlier today that included a financial update, which I will briefly summarize. Total net loss for the fourth quarter of 2016 was $71.3 million or $1.75 per share basic and diluted compared with $55.2 million or $1.42 per share basic and deluded for the fourth quarter of 2015. For the year ended December 31, 2016, total net loss was $245.9 million or $6.21 per share basic and diluted compared with a net loss of $145.6 million or $3.96 per share basic and diluted in 2015. This reflected cash used in operations of $161 million in 2016 compared with a $106 million in 2016. We continue to expect cash used in operations to increase throughout 2017. Net loss for 2016 included approximately $58.6 million in non-cash charges with stock based compensation of $48.3 million, amortization of premiums on purchased investments, depreciation and amortization and other non-cash charges. We expect stock compensation expenses to continue to increase over time. Our total operating expenses were $70.6 million for the fourth quarter of 2016 and $248.1 million for full year. Research and development cost were $183.2 million in 2016 with our Phase 3 programs accounting for the greatest proportion of R&D cost. As to reminder we share KRN23 development cost 50-50 with our collaborative partner Kyowa Hakko Kirin. Costs for our multiple preclinical translational research programs are also increasing as programs advance toward the clinic. OpEx continues to increase due to the initiation of additional late stage clinical study, manufacturing cost related to clinical supply of multiple programs, increased regulatory activity across the programs, including filings for approval, early stage investment in our US European and Latin American commercial infrastructure and patient identification efforts, general and administrative expenses to support these activities and increases in stock-based compensation expenses. Our expenses will continue to increase significantly in 2017, as a result of these activities, although the rate of increase year-over-year is expected to begin to slow down. In 2016, we recognized revenue of $133,000 in named patient sales for rhGUS. We expect revenue to remain negligible and potentially highly variable from quarter-to-quarter in 2017, given the nature of name patient sales, anticipated regulatory filings and review timelines, as well as the lengthy process of obtaining reimbursement in European countries. We ended the year with $498.1 million in cash, cash equivalents and investments on the balance sheet. We believe that we are in a position to fund all of our current clinical programs through Phase 3 trials and to potential launches. We do not have any debt outstanding. With that, I will now turn the call back to Emil.

Thank you, Shalini. As you heard we advanced each of our programs through the clinic and have made progress toward regulatory filings. By the end of 2017 we expect to have two products filed in both the US and Europe, data from two Phase 3 studies and two additional Phase 3 studies up and running. Strong team continues to push these programs through the development and regulatory process and we thank them for all that effort, this last year and this coming year. This year we will continue our preparation for global commercialization. I look forward to updating you throughout the year on our progress. With that, let's move to your questions. Operator, can you please provide the instructions for the Q&A portion of the call.

Thank you. [Operator Instructions] And our first question is from the line of Eric Schmidt with Cowen & Company. Please go ahead.

Thanks for the question and congrats on the progress. Emil, on trihep in FAOD, it sounds like you know, considering that event-based endpoint that you mentioned, is the FDA pushing you in that direction and what would the event-based endpoint be just simply hospitalizations or some composite?

Well, the FDA hasn’t pushed us, I mean, I think we haven’t met with them yet to discuss the plan. What's compelling to us is that, you know, with 50% reduction in days in the hospital is immediately important and valuable thing for patients both for their health and cost to the system. In these days in the considerations of value per patient, data like that I think would be a more compelling story when you're launching a product internationally when you talk about reduction in hospital days. So our view is just the intrinsic value that is great and question we had in doing this study was could you achieve the power that you do a study like that. and since we were able to hit it would just - a relatively small study, it gives us the possibility that a study like that would not be an extremely large study or would not take incredibly long period of time to succeed. So that’s why we are considering it. The other option was doing an exercise base study. We have thought about that you know, I think it may be simpler to an exercise base study, but it has its own issues and our view is when I look at all the options, come up with a plan, talk to the regulators and obviously between exercise tolerance and days in the hospital I am sure FDA is going to be a lot more interested in days in the hospital, just knowing their other perspective what clinical benefits it means. So we would expect that would be acceptable. We just have come up with a plan that we believe and that will make sense from time and investment standpoint.

Okay. Makes sense. Just a quick one then also on trihep in the Glut1 seizure disorder Phase 2 study, what's great limiting to getting us those data, it seems like the last patient visit occurred some months ago?

Its coming, I think we are – the thing we had is a diary based study and so we had to do make sure that all the diaries were complete and through the dairy cleaning process where you are looking and making sure everything is practiced, it took more time. We have to connect with international doctors all around the world that we're involved and that process we just wanted make sure it’s all done very correctly before we unwind a study like that. So it’s just - we want to give more time to make sure we get all right, that’s all.

Thank you.

And our next question comes from the line of Gena Wang with Jefferies.

Thank you for taking my question. As the first just a quick follow up, Emil, question regarding the seizure data, we know that data release – be released anytime soon, just wondering if the data will from initial 8-week, double-blind treatment phase or will we have more data the extension phase? And also can you remind us the statistic assumption?

Sure. So, the study will compare 8-weeks of treatment to their running period of six weeks for patients on drug versus placebo you'll see the blinded portion of the study, not the extension portion of the study really focused on the blinded portion of the study and the data we would release. The plan on statistics where the primary endpoint is, obviously we – we have two different types of seizures which is not been done, it’s a little bit different, but we just work on modeling and how to plan that and we have we think the best plan. A patient coming in the study was either qualifying because of observable seizures or absence seizures, and depending on how they qualify to get in a study that will be the primary way they are going to be assessed for the primary endpoint. So we'll use a diary for the patient or we might use the EEG for that patient. So that’s sort of the basic plan. Our expectation is then, we have about half the patients had observable seizures, about have had absence seizures, so its kind of equal group. We'll then - that will be the primary endpoint comparison to placebo. If that seizure doesn't succeed, we'll also look at absence seizures or observable seizures independently as a group, but in that subset we'll just compare each patient to their baseline in that subgroup of seizure patients to get understanding of whether we were having impact on that type of seizure absence or observable. As you may remember in the past there was a publication showing a 70% reduction in odd some seizures in patients using EEG-based method. So there's some evidence of poor UX007 and operating – and working in that indication. We want to make sure that we were not - because we different type disease we want to make sure we can capture any effect that might be occurring in one seizure type and not another seizure type. That was basically designed. So both seizures together, with the primary endpoint and then we'll look at observable or absences independently as well.

Okay. Thank you. And the another question, follow up question would be, for KRN23 adult data, I know you mentioned that it will be the most exciting data in 2017, could you share with us your t expectation for the data outcome and how does that affect pediatric filing in the case of positive data and the negative data?

So you want me to predict Phase 3 filings and you of course not going to hold me to that, right.

No, more for the pediatric filing, how is the adult data affect the pediatric filing?

Yes, when we – first when we designed the study, we designed it with more than adequate power to assure we can detect the fact, that we had good data from Phase 2, which told us how many patient would be required and we designed the study we think with ample power to detect an effect in pain, stiffness and physical functioning. So that's how we designed it. Our discussion with FDA suggested that it is possible to file for peds alone, our view was and the discussion was that if we added the adult data into the filing it would help - it would help support a broader label. However we did not have the impression that we could not file without the adult data, that the pediatric data, the effective pediatric was – but we got breakthrough therapy designation for. So our expectation is that we will talk to the agency when we see that data, but that - if the concern is that Phase 3 failed with pediatric we filed, or we think that that is still true based in our discussion.

Okay. Thank you.

And our next question comes from the line of Cory Kasimov with JPMorgan.

Hi, guys. This is Sean on for Cory. Thanks for taking my question. Just a real quick one, so if I am looking at your presentation yesterday from the Leerink conference, I noticed that for rhGUS there was a slight about the side effects, and it looks like 7 out of 12 patients end up developing antibodies to the drug. So given that this is chronic disease indications so likely need to be distrust for long-term, have you guys looked at whether or not there is an effect on efficacy or correlations on efficacy for the patient who develop the antibody and don't develop it?

Sure. So with the NOI response by the way in 7 out of 12 is pretty typical for enzyme therapy, some of them have more. We just presenting a poster down at world on our Phase 3 data more completely. And basically, the antibody targets are now particularly high. They seem to type – they seem to fade with time and we have not noticed any clinical impact at all, nor have we had recurring hypersensitivity reactions, which are pretty common in enzyme therapy for MPS 7. So at this point we don't think the antibodies have an important role in shorter-term or long-term outcome in the therapy.

Okay, great. Thank you.

And our next question comes from the line of Joseph Schwartz with Leerink Partners.

Thanks very much. And my question is one KRN23, then I have one on MPS 7. So first talk to us, when your open label bone biopsy data would read out for KRN23 and how you think this data will fit into the overall filing package and how regulators will view product profile?

Right. So for those not recollecting, we have the randomized controlled, placebo controlled Phase 3 study for KRN23 adult. But we're also doing a bone quality study of KRN23 in adults which will look at the biopsies. That data is being collecting, I think its going to be something later - of late this year, where we'll have more data on that because it’s a 48 week study, the before-and-after biopsies are 48 week. So we expect to see that data late in the year.

Okay. That’s helpful…

Now I don’t think that data – I think that data helps support the efficacy. It is another way for us to support the youth and adults. So it is one of two ways to help demonstrate the value in these patients. Accumulation does cause some pain and vague symptoms of things, but it is a fundamental measure of the bone - underlying bone quality and it is very poor in these patients. So we think its supplemental data, but it also could be additional ways to - that would provide us another a way of getting approval for the adult indication.

Okay. Thanks. And then on MPS 7 and rhGUS, what is your latest pre-commercialization or suggest about the market opportunity in terms of the distribution of these patients were elide, whether there's a favorable ROI for you to build the sales force around the world to serve these patients or you planning on some sort of partnership structure to excess people in the some less core markets?

Yes. So right now we're continue to do patient education. We've done a lot of work more in the US. Our Europe work is just kind of getting going, in South America we're starting. We haven’t really put out any patient numbers at this point, but MPS 7 we've said, we estimate it would be about 200 patients developed. So it’s obviously very small. Our goal will be to operate commercially very lean and to work on the main territories. To this point we think and I have been through this before with naglazyme [ph] at BioMarin. The truth is that for a smaller process, it’s very hard to divide it between you and partner and make that work. So he is able to run a commercial organization lead to support, they are not to go big. The value we have those will have other products in play which will allow us to leverage our investment and allow us to commercialize it efficiently. However, for certain territories or maybe distribution ships s of partnership for some places where we're not going to do with ourselves where it might make sense and we're open to – looking at those opportunities where they make business sense.

Thank you.

And our next question comes from the line of Kennan MacKay with Credit Suisse.

Hey. Thanks for taking my questions. One more on KRN23 here, on the KHK quarterly call they had announced that they had higher expectations for KRN23 to receive approval in the US and Europe. Just wanted to get a sense as to maybe where that could be coming from your conversations with the FDA and EMA? And also wanted to get a perspective on what you are sitting in the XLH registry, are you still thinking sort of US prevalence of a total of 12,000 patients and the reason I am asking it again, because in KHKs updated deck they decided about 12,000 adult patients, meant about 3000 pediatric patients for total of about 15,000 in the US, I just wanted to get your perspective on whether…

Sure…

I was sort of thinking about it right?

Yes, so feel the prevalence, you know, the rare disease problems is never very strong – perfect. The original numbers we provide were based on a frequency of 120,000 and you could do the math on the US population and come up with 15,000. We had said 12, we don’t know if there is mortality factors, some other facts, so that’s where our 12 came from. I can't really speak to their numbers exactly, but I actually don't think that those numbers are dramatically different. I think would have been in the range of variation we might expect in a rare disease population. But I think, we would say that its still - a lot patient publicly in the US compared to other things, like let’s say MPS 7 for example. So you asked about the - their view was that the probably approval was increased? We certainly feel strongly that we have a good data set and our meeting with regulators have you suggested that we have a file board and approval package. But of course, we can't predict regular and do in the process. But the EMA allowed us to file conditional on the data, they filed the data and they allowed us to file because they think that they could improve us, but as you know as things go on in an approval process, but we're confident and we have approval package, but that doesn't mean there's not going to be potential for anything happening. In the US we were still finalizing what the package is, I think the FDA has indicated they feel that including the adult Phase 3 data with peds phase 2 data would give us a stronger package in their mind and they strongly advised to focus on that, rather than filing just a piece indication. That of course slowed up the timeline for us, but the benefit of this that we would get a broader label potential off the gate. Again in the BLA, the FDA doesn't predict a provability of applications, but they do give guidance, whether this is filed or not and at this point we have a feeling that with adult Phase 3 data and peds data we would be filed, though potentially the peds data alone could be filed though. We'll get clarity and that when we prevailing [ph] meeting and then update best to that point in time. But we feel comfortable we have a filed the package one way another and we feel good about the prospects for approval. We just – we don't normally predict what that number would be.

Totally correct. I appreciative the color Emil. And maybe just a quick follow-up on triheptanoin in Glut1 DS and the Phase 3 going on there. So it looks like this is going to be utilizing sort of a patient diary and just wanted to get a perspective on some of the conversations that you had with the FDA about the inclusion of that diary and sort of what controls our - in place there to sort of ensure the quality of that data?

Yes. So we are using electronic diary here and we are - have designed the diary and focused on disabling movement disorder. Our original schedule that we included all types of events, many of which are distressing to patients, but which FDA thought may or may not meet the criteria being disabling. They want events that interfere with the patient's daily activities, that they can't do things. Although patients that say when they have tongue twitching or eye twitching or motion problems are disturbing for them because they are – its obvious to them something is going on. So what we did was look at our data and trend back to what we thought was disabling movement events. And so what we'll be recorded are disabling movement there, but we will capture other events as well in diaries. We just made this modifications and we were able to proceed. We filed that and the FDA has not still allowed us to proceed. So I think the key there is just they want to make sure we're doing things that are really powerful important what we're measuring and not something that might be thought of its more superficial. So that's the basic plan. The diary is electronic, and would be - we think a high-quality tool for tracking what's happening each day, at end of each day, how many thing have happened during the day and that will allow us to capture an effect.

Got you. Thank you very much for taking my questions.

And our next question comes from the line of Chris Raymond with Raymond James.

Hey, thanks. Emil, on KRN23 in the adult study, I know this is been discussed a bit. I know you've talked about how showing a serum phosphorus level decreases not enough you need to show these clinical endpoints and the three specifically. But can you maybe clarify the statistical treatment of those three, if you hit on one, but miss on two, or hit on two and miss on one, is that good enough or is there some higher test there statistically?

Well, our plan in the power for the study is that we want to hit all three, that’s our expectation from the power end of study. So the question is how do we approach the multiplicity? In this case we are doing - its not hierarchical, it’s not like a sequence, it’s basically, I would call the hopper procedure for those - the statisticians among you, it basically takes the worse p-value and test it first and work your way down. So it could be if we have one resolved that’s hit point PO one, two I was at miss or trend only, that’s still a positive result from clinical standpoint. However, if we use one of those type of things it will become a review issue, we have to the discussion with FDA, we have a partial resolved, what does that mean, we think its clinically meaningful. But I think it depends on the total context. But I will guarantee you having work with FDA programs they don't like to make predictions of what they are going to do based on what they see, they like to see the data and then they will tell it to you. So what they want to make clear to us and they wanted to demonstrate clinical benefit in some way in the study and not phosphate alone. And so you could argue one endpoint positive is clinical benefit, so it’s going to take a whole context of what we see to understand what it means.

Okay. Great. And then I have a follow up question on trihep. So just on the Glut1 Phase 3 movement disorder study. I think the beginning of the year you guys talked about having the beginning of that study being imminent and it looks like we've got the similar language now, can you maybe point to something that’s – are we splitting hairs here, expecting something sooner than a month or two, or what if you could maybe talk to what the delay is, if there is one?

Well, we have sites they are identified operating in both US and Europe and active in US, they are in the point of screening patients. We talk about the steady start, when a patient gets investigational product, that’s when the timeline starts. Its happening, you know we say imminent because we think it is within – and certainly within this quarter, but we expected to be relatively soon and we're - the process is ongoing right now.

Okay.

So I don’t know more than you could say.

Okay. Thank you.

And our next question comes from the line of Adam Walsh with Stifel.

Hi. Thanks for taking my questions. My first one is back on the trihep Phase 3 Glut1 movement disorder study. Emil, it sounds like the primary endpoint of the regulators have asked for, it’s little bit more stringent than the one, perhaps it was used in Dr. Michelle's original study. I guess my first question is, is it a more stringent endpoint? And then the second question is, if Dr. - if you looked back at Dr. Michelle's data that she reported it was only six patients, but can you apply the more stringent endpoint of disabling paroxysmal movement disorders, what would those data have look like? And then I have a follow-up. Thanks.

Yes, well obviously, it will be critically important to understand that and we did do that and the reduction was the same in disabling versus others and just most of the events were disabling, they were just some – a few that were not. So when you look at the percent reduction, the 90% reduction you observed in disabling, as well as others. We just lose a few events that were not considered disabling, but the majority of events are disabling and reduction rate was the same.

Okay. That’s helpful. And then also in Dr. Michelle study. I think she originally had eight patients in her study and two other patients weren’t included in the analysis. It was presented because they were non-compliant. And I think those were assessed by biochemical parameters, specifically, if I remember correctly C5 ketones, which you expect to see in compliant patients.

Right.

Will you be checking for C5 ketones in the Phase 3 in terms of compliance. Is there some way you can utilize that biomarker to you know assess for compliance or would that be useful?

Well, we will collect you know, metabolic markers. But the truth is in the pivotal Phase 3 trials, you don't get the drop off patients, you will be required include intent to treat analysis, which will include all patients. If you do the analysis with Fannie data with those two patients, you still get a very strongly positive result. She is just trying to demonstrate the two didn’t respond, why didn’t they respond, they didn’t have any drug in them. So okay, so the reason is not the drug within them and it didn’t help them, it was they didn’t take it. So it was mainly an explanation what was going on in those patients. However and then I get a - in a Phase 3 study we're going to have to evaluate all patients that receive investigational product in our analysis plan and we will - in terms of we look at the metabolic parameters, but I would say to you that it's unlikely would be able to say the FDA we're going to drop off patients, they don't have product in their blood, just not something normally allowed to do. We will look at it just in case we do have people that didn’t respond, they should have, and maybe that would give us an indication of what was going on. We are working in accordance with this oil therapy to assure that dietitians are healthy people, titrated and get on the right drug dose and it takes a little bit of work to make sure that their titration ramped up phase. So we'll do our best to assure people are taking the drug they will need to take it. We've gotten that to work in our FAOD study, patients are provided drugs for quite a long time, with the right does. So we think it's doable, but I think that's an explanation work that went on her study, but I don’t think it changes our outlook.

Excellent. Thanks so much. Appreciate it.

And our next question comes from the line of Arlinda Lee with Canaccord. Please go ahead.

Hi, guys. Thanks for taking my question. So on the Phase 3 movement disorder study, these are going to include only patients that are not on ketogenic diet. Are you expecting to enroll patients to switch off ketogenic diet or for whatever reason have chosen intolerant testers and not to be on this therapy?

Understand. So in movement disorders, ketogenic diet is not as effective and it's harder to do frankly in adults, its lot easier when your kid and people control everything you eat, but in fact ketogenic diet is not being used more routinely in the movement disorder. And so there is less of an issue than it is when you are seizures. We don’t think it’s a good idea to force people to come off ketogenic diet, we are looking for people who are generally were naïve to it, is the right way. So we don't think it should be a problem because it's understood that it doesn't work as well in move disorder phenotype, it’s also to hard apply in adults.

Thank you.

And our next question is from the line of Edward Nash with SunTrust.

Hi. Thanks for taking the question. This is Mike on for Edward Nash. And so just want to understand about the powering for the Phase 3 trial or Glut1 DS movement disorder. My understanding is that the trial is based – design of the Phase 3 trial is based on the six patients from Michelle trial, so just try to understand the power there? Thank you.

Yes. So the Phase 3 movement disorder study has 40 patients in a randomized double-blind crossover design. So its all 40 patients will get placebo and drug and they will be compared for how they did on drug, for how they did on placebo. If you remember from the Dr. Michelle study that she put people on a - in a run in period with non-end drug, put them on drug for two months, linkup the results and took them off drug for two months, the effect of the movement disorders came back and put them on drug again they came back down again. So basically there was a pretty rapid on off of stack with you on drug or not, and what we're taking advantage of the study, the fact that if you take same patient with their particular movements and put them in an on/off mode, you gain a lot of power. So the 40 patients study should be more than adequate power to detect the movement disorder than. And it sometimes could depend on what the placebo rate is, but we think at this point placebo rate should be relatively low, but the design 40 – the study was very significant with just six patient. So we think with 40 we should be more than adequate power to achieve the result.

Got it. That’s helpful. And also for the Phase 3 trial for LC-FAOD, we are against to initiating this year, just trying to understand about - because it is even based endpoint, so just trying to understand about duration and up potentially may be 1.5 years for trial?

Yes. So the duration of the study that we did in Phase 2 was 1.5 years comparing historical 1.5 to the next 1.5. We could design something like that. We haven't set a plan yet, whether it's one year or two year. What I would suggest to you in a study like this where you are talking about advance and healthcare, kids, right, which we would likely have a data monitoring board, then you know, look at the study and likely if we are showing a big separation between being in a hospital, not in the hospital, its possible that a larger study could end up shorter if that worked. But we haven't set a timeline, and certainly going to be at least one year as my expectation for that. I wouldn't expect to be less than a year. How much longer the year, it might depend on how many patients do we enroll, right, and how long we have to go to get the difference. We used 18 months that it probably could have been positive at one year, but the team is still working on the numbers and obviously we never wanted to design a study that’s barely over the line, we wanted study that's definitive and compelling. So we'll still need to do some work on the exact length. But I would assume it’s not less than a year.

Thanks a lot.

And our next question is from the line of Waseem Ahmed with Bank of America.

Hi, guys. This is Peter Stapler on for Wasseem. Thanks for taking my question. On the triheptanoin trial, could you talk about whether patients with observable or of on seizures are more frequent, it was one group more or less difficult to recruit, and how many patients have an overlapping presentation of the symptoms? Thanks.

So we'll start with the last part, one is very interesting and unusual and that these patient can have one, two or three different sites of seizures in same patient ongoing at different rates. So it’s pretty complicated. Absence seizure is actually more common, a broader fraction of absence, but the generalized seizures people think of is, is more concerning for people. Although I think both of them suggest their brains are not functioning well and they are not good. So if you look at - there some paper to look at the distribution, but absence seizure is probably a bigger fraction than observable, but observable people pay attention to work on. The challenge in recruiting is not so much about – for the instance in the seizure type whether they are on ketogenic diet are not. And in general the observable seizures patients get put on ketogenic diet very aggressively, whereas absence they weren’t as aggressively used in ketogenic diet. So we had – we would actually turn out to be easier than worse on some of absences patient because they weren’t – they are taking meds, but not ketogenic diet. So that’s more about competing therapies and it was about the problems exactly of the type.

Thanks.

And our next question comes from the line of Matthew Harrison with Morgan Stanley.

Hi. This is Cyrus on for Matt. Thanks for taking my question. Can you remind us what you to see in the pivotal study of ACR and given your discussions with the EMA, what you see as the regulatory bar for approval?

So the ACR program is designed very similar with the Phase 2, the difference is we enrolled only the patients that had greater than 200 meter walking ability. So we enrolled a stronger - the stronger half of the patients that we're in Phase 2, who has a bigger effect and the more powerful effects, so we've enriched for the patient who should show us the best difference. what our EMA discussion suggested, that if we simply replicate what was observed in the Phase 2 study if that would be filed for us, nothing we said before that we didn’t have to do something more, we just can replicate what we saw in Phase 2 and the Phase 3 studies and we should be filed. That the primary endpoint in this case is an upper extremity composite muscle strength. There is data - there are endpoints are lower extremity and there's also the functional activity scale endpoints which we believe were powered worthwhile. The hope would be to have a primary endpoint with muscle strength and also has supporting data from the patient reported for the venture activity scale that would give us I think the best label. But our view is that we can show the strength differential that we saw before, that we would be potentially filed with that data. So that’s what we got from EMA.

All right. Thank you.

And our next question is from the line of Yigal Nochomovitz with Citigroup.

Hi, Emil. Thanks for taking the question. Are you still searching for new CMO or is that suspended right now? Thanks.

As I - what I – when since I left last time, what we said was we're going wait for few months and because we have so much going on and we've obviously executed well on the development side, the teams have done a phenomenal job and moved things forward. We've initiated a search for CMO, but we're not going to a rush into, we want the right person. Obviously we have lot of work going on and we need help. We have added some people to senior level, which we haven't disclosed. But we've actually bolster our team and I think that we are – I think we're good shape right now. But we obviously need a high-level clinical leader to help us to the next level and that search is ongoing.

Okay. Thanks. And just one quick follow-up on the seizure trial. So as I understand you’ve shown the data for the absence seizures per single dose that was a 90 minute experiment, could you just comment on how you believe that efficacy may translate both to the observable seizures, which you are looking at, as well as in terms of duration of effect because the current study is obviously an eight week endpoint? Thanks.

Yes, so the study you're referring to was not our study, it was an investigator initiate study and that study showed a 90 minute, but if you look at the paper, they also followed up with a three-month assessment, which show the same effect we're recurring after three months. So it showed both a 90 minute and three months very similar. So we think that the effect to sustain certainly in absence seizures that data really speaks to absence, I think the thing you have to understand by Glut1, is that the brain is not functioning because it’s running out of energy. If you're fixing the map of stations with regard to replacing the energy source and restoring brain function with regard to absence seizures – as you are really helping the brain in general, our expectation is that it would translate other types of seizures which are also related to declining energy function. However, we don't have data show you on observable seizures at this point in time. But we will have both types of seizures in the study and that will give us a chance either replicate the absence seizure thing and also get an idea of whether verbal generally seizures are also improved.

And you make connection between the movement disorder results in observable seizures or is that not appropriate?

Well, you know, and I don’t know if you know analysis there, seizure is our kind of a cortical, surface-of-the-brain phenomenon, but the movement disorders is the middle of their brain, basal ganglia type problem, like Parkinson's disease are affected. Those are high-energy neurons in adults. Those are the ones that coordinate your movement in which is very complicated while coordinating one neural signaling because uses so high-energy that’s why it tend to be in adult. But whether the cortex or the basal ganglia, what we're talking about is inadequate energy stores and efficiency which leads to inadequate neurologic functions. So I think the same thought – phenomena is happening it just depends they way you are talking about the surface of the brain or deep in the brain, that depends on how old you are and what you doing.

Okay. Thank you.

And our final question comes from the line of Carol Werther with H.C. Wainwright.

My question. I was wondering about the LC-FAOD study, just in terms of the side effects and also whether or not people were able to come off the MCT oil?

So the FAOD Phase 2 study, you are talking about?

Yes. Thank you.

So in that study the patients 27 or 29 were on MCT oil as their energy source, during the period where they are having events, that they were on that during that period. When they started our studies then they came off MCT well completely, and crossed over on the triheptanoin, so they switched that part, but the rest of their schema for their diet and systems were the same. They just switch for MCT to try out. So when I look before and after what you are really looking is what they were doing while they were on MCT versus what were they doing while they were on triheptanoin, does that help to clarify?

Yes. It does. And then it seems that most of the side effects are G.I. related, but you mentioned that you can manage that by adjusting the dose with food. Can you just explain it to me?

Yes. Well, I don't know, if you go to Italian restaurants, but if you eat too much of the bread with olive oil, you can get your stomach very upset, at sometimes do that. But the truth is you need a lot of oil in your stomach, it gets your stomach going, it will get your some active gastrin and so that’s kind of what happen. So we have to kind of work them off on the dose. The key though is we just take straight oil at shots, as you try that all by the way it would make you sit to. So the key to that is mixing it with a food that can also sort of multiply like non-fat yogurt or add some things that will multiply the oil and break it up, so it doesn't sit your stomach like a ball and then slide on through as one will little chunk. So if you mix it up with food, don't take it in shot and titrate them up, that usually gets people refined than they figure it out. If they start and try to take it like a shot like NyQuil in a little cup and take a shot that will cost stomach upset, its is not because of – it really could be any oil, you try to any oil, it will cause you the same kind of problem.

Okay, great. So then overall, it’s very well tolerated, if you moderate some of these things?

Yes, you just have to manage, d titrate it up, mix it in the right way, not take it…

Okay. Thanks very much.

Ladies and gentlemen, this concludes our Q&A session for today. I would like to turn the call back to Ryan Martins for final remarks.

Thanks everyone. This concludes our call. A replay of the call will be available shortly. If there any additional questions please contact us at 844-758-7273 or ir@Ultragenyx.com. Thank you.

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. And you may all disconnect.