Ultragenyx Pharmaceutical Inc. (RARE) Q3 2016 Earnings Report, Transcript and Summary

Good day ladies and gentlemen and welcome to the Ultragenyx Third Quarter 2016 Financial Results and Corporate Update. 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. [Operator Instructions] As a reminder, this conference may be -- being recorded. I would now like to introduce your host for today’s conference Mr. Ryan Martins, Vice President of Strategy and IR. Sir, you may begin.

Thank you, good afternoon and welcome to the Ultragenyx Pharmaceutical Financial Results and Corporate Update Conference Call for the third quarter of 2016. We have issued a press release detailing our financial results which you can find on our Web site at Ultragenyx.com. I am Ryan Martins, Vice President of Strategy and Investor Relations. 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 statements regarding plans with respect to our translational research program, the expected timing of release of additional data for our product candidates; plans to initiate additional studies for product candidates and timing and design of these studies; plans regarding ongoing studies for existing programs; the expectation of increased expenses over future quarters; our belief about adequacy of current cash resources to fund future operations; expectations regarding the adequacy of clinical data to support marketing applications and approvals of product candidates. Our intent to file marketing applications and expectations regarding timing of receiving potential approval of product candidates. These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical drug development process, such as the regulatory approval process, including with respect to the MAA we filed seeking conditional approval from EMA with respect to Ace-ER, whether the Phase 3 results for Ace-ER will in fact confirm or mirror the results from the prior Phase 2 study, whether the FDA will accept the planned BLA submission for KRN23, the timing of our regulatory filings and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations and the availability or commercial potential of our drug candidates. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed on the forward-looking statements, as well as risks relating to our business, see our Quarterly Report on Form 10-Q for the quarter ended June 30, 2016, filed on August 19, 2016, our quarterly report on Form 10-Q for the quarter ended September 30, 2016 that will be filed soon and our subsequent periodic reports filed with the SEC. I will now turn the call over to Emil.

Thanks Ryan and good afternoon everyone and thank you for joining us. I will start by discussing our recent progress and milestones and Shalini will give go over the third quarter financials. We've continued to move forward our programs in the third quarter of 2016. We are pleased to announce positive data from a number of KRN23 studies at ASBMR in September initiate our second phase three study for this program. We continue our discussions with U.S. Food Drug and Administration about our regulatory path forward for KRN23. We are advancing our earlier stage translational research programs particularly through our partnership with Takeda. Let me start with KRN23 for XLH. In September, we presented positive data from number of our key studies in our KRN23 program including the ongoing Phase 2 studies in pediatrics and adult patients with X-Linked Hypophosphatemia or XLH and the ongoing Phase 2 study in patients with tumor induced osteomalacia. The data demonstrates the KRN23 can have a sustained effect on phosphate wasting and the underlying cause of the disease. And they can also reduce the following disease and improve other functional limitations. Adverse events were consistent what has been previously observed for KRN23 further treatment of XLH and TIO. With the Phase 2 XLH, it enhances and following our breakthrough therapy designation for KRN23 for pediatric patients aged 1 and older with XLH. We have been in discussion with FDA about accelerating our regulatory pathway for KRN23 in the U.S. After meeting with FDA, we now expect that the data from the pediatric randomized [placebo] [ph] controlled Phase 3 will no longer be required to file the U.S. biological license application or BLA. And as a result of that, we plan to submit a BLA and the FDA in the second half of 2017, significantly sooner than previously planned. The final detail contents, the clinical study data required for the planned submission still under discussion with FDA, we will provide an update when we know more. We are still moving forward with the Phase 3 study in pediatric XLH patients, which we recently initiate because it will have importance value to the program. So not necessarily required for U.S. approval, we believe the study will be necessary to convert our possible conditional marketing authorization to full approval in Europe based on our EMA discussion. We also believe that will be value for reimbursement to compare the impact of KRN23 on normalizing phosphate level with what is achieved with conventional therapy and the impact this has on bone disease and physical function. As a reminder, the pediatric Phase 3, the randomized open label clinical trial study that will roll-up approximately 60 patients, we will compare the efficacy and safety of the KRN23 to oral phosphate and active vitamin D. The study will evaluate pharmacodynamic assessments including serum phosphorous as well as changes in rickets, growth lost in height, walking ability, fatigue and physical function and patient report outcomes assessing pain as well as safety plus the KRN23 update at this point. For the ACR program, we have been working with the EMA on our conditional marketing authorization application for ACR and GNE myopathy. We are scheduled for an oral explanation to EMA on December 8, expect the one remaining major objection related to the clinical interpretation of the Phase 2 data. There are explanation meeting and the closed meeting and we expect our next update in the program will be at the time of the CHMP opinion, which we currently expect by the end of the year. Now, turning to rhGUS for MPS 7, while we continue to advance program to our marketing application filings in Q1 of 2017; we are also continuing to work on obtaining or expanding patent coverage for rhGUS. And last month, we were issued patents for both composition and matter immersive treatment for rhGUS and patents will expire in 2035. I would like to go through some upcoming milestones now for KRN23, in addition to the U.S. filing in the second half of 2017. We plan to file conditional marketing authorization in the EU for XLH around the end of 2016. In the first half of 2017, we expect data from the Phase 3 study of the adult XLH patients. We enrolled 134 patient studies, which will valid change in serum phosphorous levels, pains, stiffness, physical function and safety of monthly KRN23 compared with placebo. And moving on to rhGUS, earlier this fall we met with FDA and the EMA to discuss our plans to submit filings based on the recent Phase 3 study result, following these discussions, we plan to submit regulatory filings in the U.S. and Europe in the first half of 2017. For UX007, this year we expect the 78-week data from our Phase 2 study in long-chain fatty acid oxidation disorders. We will be releasing data comparing major medical event rates approximately 18 months before starting the study and after UX007 treatment. We will also provide longer term safety and exercise tolerance data. We plan to initiate around placebo-controlled Phase 3 study in approximately 40 patients with a movement sort of phenotype of Glut1 DS by the end of the year, in the study moving to Therovance will be recorded by a patient diary. In the Phase 2 seizure study, the last patient visit recently occurred, the data now being prepared for an analysis and because this study is diary based study, we need to verify them before we can unblind the study. The result, we are now expecting to have the data from the study in the first quarter of 2017. Lastly for ACR, the addition of the upcoming 2016 CHMP decision that I mentioned previously, we also expect data from our fully enrolled Phase 3 study at ACR in the second half of 2017. Now, I will turn the call over to Shalini to provide overview of our financial results.

Thanks Emil. We issued a press release earlier that included a financial update which I will briefly summarize. Total net loss for the third quarter of 2016 was $64.9 million or $1.64 per share basic and diluted compared with $39.2 million or $1.03 per share basic and deluded for the third quarter of 2015. For the nine months ended September 30, 2016 net loss was $174.6 million or $4.46 per share basic and diluted compared with a net loss for the same period in 2015 of $90.4 million or $2.51 per share basic and diluted. This reflected cash used in operations of $113.3 million in the first nine months of the year compared to $65.5 million in the same period of 2015. We continue to expect increases in cash used in operations for the balance of the year and into 2017. Net loss for the first nine months of 2016 included approximately $42 million in non-cash charges with stock based compensation of $34.8 million, amortization of premiums on investment securities, depreciation and amortization and a non-cash license fee from a collaboration arrangement. We expect stock compensation expenses to continue to increase over time. Our total operating expenses were $65.9 million for the third quarter of 2016 and $177.6 million for the first nine months of the year. Research and Development costs accounted for $48.7 million or approximately three quarters of our operating expenses during the quarter. Our three Phase 3 programs account for the greatest proportion of R&D costs. As a reminder, we share KRN23 development costs 50:50 with our collaborative partner Kyowa Hakko Kirin. Costs for our multiple pre-clinical translational research programs are increasing as programs advance toward the clinic. OpEx continues to increase due to the initiation of additional late stage clinical studies , manufacturing costs related to clinical supply of multiple programs, increased regulatory activity across the programs, including filings for approval. Early stage investment in our U.S. and European 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. This quarter the company recognized revenue of $111,000 in named patient sales for rhGUS. We expect named patient sales to remain negligible for the balance of 2016 as well as into 2017. Given anticipated regulatory filings and review timelines as well as the lengthy process of obtaining reimbursement in European countries we expect little to no commercial revenue from these programs in 2017. During the third quarter, we received approximately $74 million through the Takeda transaction and at the market offerings. We ended the third quarter with $472.6 million in cash, cash equivalents and investments on the balance sheet. Following the end of the quarter, we received approximately $51 million from the Takeda second tranche and at the market offerings. A portion of these proceeds will be used to fund the initial development of the undisclosed preclinical license products from the Takeda collaboration. 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've heard, we made progress in both the clinical and regulatory front this quarter. We pleased to be preparing marketing application filings through to the EMA this year and for U.S. approval KRN23 in the second half of 2017, which is earlier than previously expected. We're also moving forward with filings for rhGUS and European filing for KRN23. Having been in the business for some time like economists say this is an extraordinary moment to be in position to file two more product marketing applications in the next few months while still prosecuting a third application all at the same time. This is incredible effort and this is a strong testament that we are still in work at the team here at Ultragenyx. I want to thank them for that effort. And it has been amazing to see. 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 comes from the line of Eric Schmidt from Cowen & Company. Your line is open.

Good afternoon and congrats on all the progress. Emil, it sounds like you've had some pretty productive conversations with the FDA on KRN23. Should, we assume that all you need to achieve in the adult study in the first half of next year is just the primary point the change in serum phosphate and that alone would allow you to receive a broad label?

Well, now the FDA in the pas Eric -- it's a good question, FDA in the past has required to have a clinical endpoint also in the study. We have been talking about the pain endpoints and there are also other sectors, definite physical function that are important in there. So our expectations we -- the phosphate alone would not be sufficient based on our touch with FDA. However, we have powered the study and enrolled it well and I feel comfortable that we have enough power to hit technical clinical end points that would be sufficient. But, at this point, we could not just file phosphate data alone.

I'm looking at the rickets endpoint in the Phase 2 pediatric study and saying that's good enough?

Well, they might say that is good enough for the piece indication but you are asking question for the whole --

Yes, I was. Okay.

So for these inclusions the Phase 2 might be enough but to get the adult label, they need to see some clinical results in that Phase 3 study.

Okay. Then, just a quick follow-up on ACR, are you able to disclose what at the oral hearing tomorrow is about in terms of the one remaining issue?

Well, we talked about it being about the replication of the Phase 2 data. I think we have stated before remember this was -- I spoke Phase 2 study, but we didn't declare a primary endpoint. We filed but persuasive statistical [indiscernible]. It's really about the clinical interpretation of those results. And that we are talking through. I can't really say anything more than that that's what we are talking about the main reason we have disclosed at this point because the agenda got caught out, so it's a publicly known that we are going to have a discussion with them. But, that's what we are talking about. And I think the essence is really around the fact that it was a Phase 2 study. But, our feelings and filing early was that the data were strong enough to warrant a positional marketing authorization, however, regulatory authorities will make their decisions and we can't predict that. All right, just to remind you, we pressed to have the Phase 3 as well, so one way or another, we are moving forward. But, we will find out -- you will find out about the opinion when it comes out.

Great. Thanks and good luck.

Thank you.

Thank you. And the next question comes from the line of Gena Wang from Jefferies. Your line is open.

Thank you for taking my question. So, for the KRN23 pediatric Phase 3 trials, it seems there is no prescreening, more severe patient was -- with such a ricket score over 1.5. And also primary endpoint where the RGI-IC score at 40 weeks, which seems shorter than the Phase 2 trial. Are you comfortable that you will be able to capture the bone improvement with this trial design?

Yes. The patient still have to have rickets on x-rays to be in the enrollment study. But, based on the data that we have to-date on the 40-week versus 64 weeks, 40 weeks has the majority of the fact that already had happened, 64 showed somewhat more but it really appears over the nine months the effective KRN23 is -- really is happening and we think that makes the more sense frankly. So, we are pretty comfortable with the design of the study based on who are enrolling, do need to have rickets and the fact that mostly that happens by nine months.

Okay. And I have one quick question regarding the trihep, just wondering, we will consider earlier filings for Glut1 disorder with seizures, since you have a data in a few months, will the data from movement disorder won't happen for like a few more years?

It's an important question. I think if you recall from -- maybe you don't recall but from before we -- as the FDA the study design 3 to 1 randomization et cetera was really at the Phase 2 study and our discussion with them that they would likely the Phase 2 plus the Phase 3 study in order to file that was what the discussion is. So, I have no reason to believe they would allow to go faster at this point than the seizure data. I would agree these seizures are important but the design of the study was really Phase 2 in structure and I think that's probably what's the difference would be. However, no matter what the situation is, we are looking at our actual data and always do the best we can from a regulatory standpoint to get our products to patients promptly.

Thank you.

Thank you. And our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is open.

Thank you very much. Your press release says that you will continue to discuss the details of the planned BLA submission with the FDA. So I was wondering if you can tell us what remaining issues you and the agency need to continue to discuss. Are there particular areas of uncertainty that still need to be resolved and how critical are they?

The main thing we would need to do is conduct a pre-BLA meeting them essentially to talk through what are the elements of a filing. What label we are seeking and what we are trying to get. And I think some of that depends on discussing the data we have and the other data that we will have and come up with an understanding because the disease has both pediatric and adult patients there is a lot of other issues to discuss. And we just want to -- before we know precisely what would need to be in the filing, we want to have that pre-BLA meeting and they held it down. So that’s what we are going to be talking about the extent of the data that we are going to include in the BLA, what that data will provide for us from our labeling perspective assuming it gets approved.

Okay. That’s helpful. Thanks. And then, did the FDA say that there is anything in particular they want to see in order to give you a broad label including P’s?

Well, I think that the -- from before the adult Phase 3 is filed against the adult label and for P’s then we have what we are filing -- we will be filing half of some parts of the Phase 2 data we have plus some other submissive data we have from under five study and some other studies that are ongoing with KRN23. So that our number of smaller components right and we want to make sure that we are getting all the age groups and then we are getting the right kind of label with the set of data. So because there is different cost of data and different groups, we just want to -- we need to work that out with them in a pre-BLA meeting. And we didn’t want to disclose the specifics yet until we really nailed it down exactly. We just thought most important is to give you the update that Phase 3 P study was required which has the most material effect on our timeline.

Great. That’s very helpful. Thanks for the added color.

And our next question comes from the line of Brittany Turner from JPMorgan.

Hello? [Corey] [ph] one of our associates, hello?

Yes. Can you hear me now?

Yes. I can hear you, yes.

Okay. Hi. This is Brittany. Just a follow-up on BLA for KRN23, did you say that you would anticipate including some open label data from the ongoing Phase 3 study for P?

No. What I said was, we would figure out what data we have from our Phase 2 that needs to be included with this ongoing study. We have under five study. We have the adult study. We just need to talk through those details and what would be included in the filing, there is a lot of pieces, and we just need to talk it through. And when we have that clarify from a pre-BLA meeting, we can then talk more about it. So we are just making points that finishing and completing and having an data from a pediatric Phase 3 is not required, so that changes at timeline and when all that can be put together. But, when we have a pre-BLA meeting that then we will be able to nail down exactly all the pieces and make sure we can provide precise and accurate update for the investors.

Got you. Okay. And then for the Phase 3 movement further study, what are some of the other end points, you will be looking at in addition to the patient diary?

Yes. So the diary we think is the most -- has the most random -- strong fact that we saw. But, we are also looking some other no logical scale but in addition, we are going to look at Cognition using a test CANTAB test which we used in the other programs. So, Cognition some other scales will be looking at walking is typical. We see that -- should be get posted, you will see the various end points they are included. It does those events is going to look at other aspects of brain function that’s exactly one patient.

Okay. Got you. Thank you. That’s helpful.

And our next question comes from the line of Chris Raymond from Raymond James. Your line is open.

Thanks. Just another question on trihep, if you don’t mind. On the Glut1 DS study that we will see next quarter, I know you guys have talked about having patients with both absence seizure as well as tonic clonic seizures that more readily captured by diary. But, I wonder if you could maybe help us understand a little bit better the trial design, how you are balancing the types of seizures between treatment and control and how you intent to monitor, especially for absences seizures rigorously enough to see a difference?

Yes. So, the study basically has essentially two inter first-arm, one arm looking out at the diaries and observable seizures. But, being in the study there are some patients who may have asthma and some patients will have both measuring in addition to the observable with diary we are measuring by EEG everyone as well. All the absences patients will be scored half of the EEG, so use quantitative EEG to look at the number of FICA then on EEG, reporting after treatment, which is very comfortable what’s been published already in these patients that they have a spike data and you can count-off essentially the number of events per hour and look at the reduction. So, we think that the -- that will be pretty accurate, so the design there will -- we will look at the combination of the decrease in the [indiscernible] seizure, the patient could contribute to the observable only or they contribute to the absences. We will also look at those groups separately, observable separately and absences separately as well allowing us accretive our ways to wins. You could win, if overall frequenting seizures occurs or if not we can also look at just observables or just absences as another way from the study to come out.

I’m sorry, I assume because it’s 3:1 to randomize, you have taken pains to make sure that there is an appropriate distribution right between control and treatment, is that correct between absences and more detectable seizures?

Yes. The challenge of course was a small 3:1 as the group is extremely small, right? So, stratifying with a very small 3:1 is actually challenging. They now [indiscernible] take the observable -- the overall seizure will compare to placebo but the individual groups will look within group as the first one, because the number of placebo’s could be very few. So you hit on a very physical point. So we have actually managed that by looking within group when you are looking at say one type of seizure, let’s eliminate the issue of having like a very small placebo group potentially doing the results.

Okay. Thank you.

Does that help you?

Yes. It does. Thanks.

Thank you. Our next question comes from the line of Adam Walsh from Stifel. Your line is open.

Hi. Thanks for taking my question and great news on KRN23 and pediatric indication, the early filing that’s terrific. Emil my question is kind of high-level for you. It looks as though in the next year, year-and-a-half, you are going to be a commercial company with potentially multiple products on the market. And obviously, in the political season, we hear and really just a general backdrop of investors, we hear a tremendous concern about drug pricing. When it comes to orphan drugs obviously the price tags need to be high to get a return on investment. But, alternatively people get concerned if there is an access problem around those drug? As you -- as we come through the political season and the talk about drug pricing has really heated up, can you just speak a little bit as you move toward commercial whether or not your use at all have changed on drug pricing, one way or the other? And how do you think about it? Thank you.

Sure. Happy to do that. I think it has been a hard topic and we have been very thoughtful about this. We have been talking about this for a long time by the way since we are a Steris A company. And we think very carefully about pricing and think about a number of factors, experience of the disease that would be a benefit, treatment modality and the size of the market. And we also like to make clear to investors that price alone doesn’t determine the revenue. It’s penetration of the market and we have seen a number of rare disease that are priced very high. But, then penetrate maybe only half what it should have been in the U.S. and maybe 10% in Europe. And we think that’s not a good model for maximizing revenue. And so, we want to be smart about how we price that, we can actually maximize the revenue for the program and also manage the access, if we are getting substandard access and creating price needs. We are not doing the right thing for our patients and that’s not the right thing we want to be doing. We do believe though that managing pricing in an intelligent way and basing it on value and also understanding the needs and how the drug will be used that we can optimize revenue and would be better for patients as well. What really makes the pricing decision zone until we know what our private label look like in the complete data set, but, we are ready to ride the best way to optimize the patient access and global revenue potential. And I think we have been talking about this for a long time. So not concerned about how we make first ever drug for patients that have no treatments at all and we want to develop drugs that are important changes for the care of those patients. And I think in that setting patients will get treated and we will be smart about how to price to make it that we can penetrate not just U.S., but the global markets and maximize the revenue for patients while maximizing access for patients.

So what if you don't guess right initially, what if there is an excess problem? How would you kind of address that?

Yes, it depends on the territory. First of all, obtaining adequate access, we think is an important part of the equation of what you do. So in the U.S., we will clearly and I’ve already said in the past, we will have patients for programs to help assure that patients who don’t can't get on treatment for one reason or another get access to therapy. And other countries we’ll work through with local local ministries, strategies to help provide access to drugs in a way that allows us to maintain a global price band, while also providing access opportunities for patients. As a company, we don’t want to see a bunch of patients not getting treated because of financial reasons. At the same time, we have to maximize revenue, and we’re going to be very thoughtful putting those programs together. But our goal is to maximize global access and revenue potential.

Excellent. Thank you.

Thank you. And our next question comes from the line of Arlinda Lee from Canaccord. Your line is open.

Yes, Arlinda.

Hi, guys, thanks for taking the questions. I guess, on if I have to know and can you maybe walk us through expectations for what are you hoping to see in the future control data. And I guess, just given the different kind of qualitative features and improvement, how does that exactly get measured or how would you rate those things and taking that to the next step, how might – what might a Phase 3 look like?

Okay. Arlinda, you’re talking about the seizure study, the Phase 3 – certainly the Phase 3 movement study?

The seizure?

Seizure. So our view on the seizure study was that, we were primarily in that study to help support the indication of seizure, so you’re assuming it's positive and that we reduce the Glut1 as the primary study to drive the approval. We might look at doing some other studies with diet known as an add-on therapy to ketogenic diet. We have been doing some ISPs in that regard and it is – it requires some thoughtful management in order to do that. But that might be some additional data we collect, but not a controlled study. So our plan at this point from a regulatory strategy standpoint is a Glut1 movement disorder, randomized controlled 40 patients study. And then this study, their seizure study, and those two together being the primary efficacy datasets for filing and supported by some other ISPs or potentially a combination study as well, which we think might be important since there's quite a few Glut1 patients who are on ketogenic diet. Does that help you?

It’s helpful. I guess, maybe a follow-up to that is, what you think you might require or not require in terms of a head-to-head study versus ketogenic diet?

Well, I don't think we're really required to – head-to-head study, and here's a problem. You can't really blind a head-to-head study, right? You can't blind it, because you can't blind the ketogenic diet and the use of it. So we can't really do a blinded study, and therefore, doing diaries, seizures in a non-blinded controlled study, it has potentially some value, but we think it’s complicated. We did this study, which is placebo controls, which we think is easier to do. But view to do but 3 to 1 randomization is to try to reduce the questions of placebo exposure to patients. I don't think doing ketogenic head-to-head is we're doing. I think there are very different therapies and we would be used differently. And I think if we're demonstrating, an effect, if we’re demonstrate an effective management seizures, I think doctors will have several tools in the tool box to use. And some patients might not want to try a ketogenic diet or might try that first to see how it works for them and if it doesn't do, what they need, they can go to ketogenic diet. Several people who try ketogenic might not want to stay on it and they come off and try to have. But I think we'll look at this is the way to manage the disease, and if we can do with some work to collect how they work together then it would be, we’d be able to provide some guidance that turns out to be beneficial that how combination might work. And I'd look at this is the way seizers are managed today. Doctors have a series of drugs in approaches, and they're mixing and matching those approaches from – if the seizure effect is significant with triheptanoin, I certainly would have expected this is so much easier to apply to patients that it would be utilized frequently in that settings. But we don't know there are relative efficacy in the various types of seizures and that's data we're going to have to come out. But I don't expect us to do a head-to-head study at this point.

Okay. Thank you very much.

And our next question comes from the line of Kennan MacKay from Credit Suisse. Your line is open.

Hi, thanks for taking the questions. This is Slanix Alex on for Kennan and congrats on the progress. A quick question regarding KRN23 and the eventual labeling. Why are the major designation does for the patients who are ages one year and older. At FDA model there was a lot of physician feedback advocating for treating patients basically from birth. And I was wondering how by that being incorporated into any discussions you might have at the FDA during your pre-BLA meeting and then what the feasibility of that might be?

Yes. So we haven't had a real discussion about from birth at this point. A lot of physicians have not really treated patients even in current therapy until their age two when they become or at the time of being weight bearing. So the one-year cut-off has to do with when kids are to walk and that's when they put stress on their bones, and that's when the rickets become more of an issue. So we think from an efficacy standpoint that makes sense. Going down to birth, I – honestly, I don't think that's a big leap. But I think we would need to complete more data in our five study and Phase 3 would have more data in the younger population and then it would make sense to step once – step further. From a labeling perspective, we don't know precisely if there’s going to be one enough BLA label or not. I would say, in a lot of the rare disease programs, we've done when we've done under five patients somewhere in the program. We've not had any age limited at all. So the question is whether one-year-old is enough to bridge to a – a newborn or not, but that’s something, I think, we'll have to figure out during review.

Okay, thanks. And the question on triheptanoin. Just help us set expectations for the upcoming FAOD data set. I wanted to ask if you had previously guided to, or can maybe comment on whether the trial has been powered for statistical significance, or whether even a trend towards benefit might even be enough to make an assessment regarding moving the program to Phase 3?

That’s a good question, and we couldn't know for sure if it was adequately [indiscernible]. I could save from before, we have the retrospective study we did. There was a 20-patient study we published. And that did show a – to simply significant reduction in the number of days in the hospital, but did cover a longer period of time. So this study is covering only 18 months, which means a lot fewer events. So we didn't really know if we’re powered or not, we couldn’t be certain, because we wouldn’t know how many patients – how many days in a hospital or how many hospital patients people would have good enrollment study. So it's really not necessarily powered. What I can say is that, what we did say previously when we had the six-month data is that, there was a trend toward a reduction in an event. But you don't need statistical significance actually. You can make friends on how the study look. We will look at the data in the reduction and understand, if there's a reduction, how big is it. And from that, we can try to power up Phase 3 study if we were going to do one of the event-based data, because right now we've been talking about exercise it’s hard and the patient report outcome type study. The event study potentially ends up being larger and longer. However, an event-based study also would be very powerful from a standpoint of reimbursement, we were just talking about cost, because, obviously, if we can show a reduction in date from the hospital, right, that's a really clear driver for value in a program and driver for patient value. And so when you look at the data, statistic different or not, and we will interpret the values and prediction regarding what the reduction event is and how meaningful is it and make a call and then what's the right move forward for the program.

Okay, great. Thanks. And just a follow-up on the – one more question on the upcoming dataset. Given that the patients are going to have aged pre versus post, I have to know in treatment over that 18 months span on both ends, and given that the number of events tend to decrease as these patients ages for more of a natural history perspective, how might that can sound the results?

Yes, it is true that over time patients can have a reduction in the events. However, I don’t think that 18 months is a really big aging factor timeframe. If you look at our original retrospective paper, that was one of the potential critics that we had patients on who had been on standard of care for like five years, or more, and some of them want to tie-up for five years. And the question would be, well, it could be just getting old be the factor. And we did a cut of data just two years before, two years after, where the aging would be less important, and you still saw the same treatment effect. And I would say, if you look on a case by case basis, there’s definitely patients who crossover and try up and – are not having as many events. And so we think that aging could be a factor, but the design of the timeframe here, I don't think would be an important factor in a reduction of the [indiscernible]one.

Got it. Understood and great. Thanks for taking the questions and, again, congrats on the progress.

Thank you.

Thank you. And our next question comes from the line of Heather Behanna from Wedbush Security. Your line is open.

Hi, thanks. Just a quick follow-up on the Glut1 study, the seizure study. Just as far as the timing of the data, I was just curious if there was any delay between screening and randomization or it's just the amount of data in the diaries and the amount of time it’s taking to process those data that will account for that delay total early next year?

Well, in the design on a patients screen, they go through a multi-week period where they get a baseline and then they get randomized in this eight-week and we then they go on a extension. The main reason is, we have a lot patient visits, as we said already is near or simply, because patients diaries come from patients, right, as you're doing across to verifying all the data any questions that come up have to go back to the patients themselves not just to the doctor – by the doctor. So it just takes more time to get through that process to make sure, we got everything right. You don’t want on blind setting once you’ve got everything tied. So we just want to make sure we get it all type before we blind the study, because you want them to be considered important for seizure label and potentially we are filing at some point in the future with those positive movement study.

Great. Thanks for the color.

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

Hi, congratulations on the progress of KRN23 and that was – my question was just related to that. I know you said, you’d filing in the second-half of 2017, just curious about what additional work I need to do ahead of filing rather than filing perhaps a little bit sooner, what’s remaining to be done on that? Thank you.

Well, so by eliminating the Phase 3 peds that means that we don’t have to wait to enroll that and treat for a full nine months, et cetera, right, that's what took the time. The adult Phase 3 now is fully enrolled and we expect a result in the first-half. We’ll also have a data for all 52 patients, week-54 will have more data on the under five study. And so there's a bunch of different things ongoing at the same time, that's what we need to talk to the FDA about in a pre-BLA way understanding the package and understanding what label we would get for various packages. So setting the timeline precisely requires an understanding of what the packages will provide. And obviously, our best goal here would be to launch with a complete label and a good label and we want to do that with make sure we have the right data in the package. So the timeline is based on the need to request and conduct a pre-BLA meeting, the completion of some of the data that’s ongoing, and then the time for preparing a filing and which take sometime, as you know, and getting it in. So that’s where the timing comes right now. We’re going to have more precise understanding of what data is in and what label we’re going for us and after we have a pre-BLA meeting. We just didn’t want to provide Liisa the fine details yet until we really have to kneel down with the FDA.

Okay, that makes sense. Thanks for the questions.

Very good.

Thank you. And our next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is open.

Yes. Hi, thanks. If I could just ask previous question a little bit more specifically. With regard to KRN23, if it turns out to be a developed study, doesn't end up getting its endpoints. Does that mean that that the FDA is going to think twice about allowing you to file in pediatric? Are these population is just different and that wouldn’t impact the timing for filing pediatric? Thanks.

Yes, I think the indications are somewhat separate. I don't think having not having an adult Phase 3 would mean we couldn't file for peds. So I think that having adult Phase 3 would allow us sort of file for a broader label, right, that’s kind of the main reason for it. The data we have for peds has already achieved license therapy designations that gives you some sense of their view of it. The question we are having is, what – how much data we have to put in to get the best appropriate and best label. So I feel Phase 3 would – I don’t think would prevent us from filing for peds. But I'm – I think our study design is down, I think we have a pretty, it’s heavily involved, I think that we feel pretty comfortable with the Phase 3 study that is just to be specific. I don't think it’s require for peds filing, we just think it's better to have it potentially. So we’re looking at those options and we’ll talk to the FDA in a pre-BLA meeting in more detail.

Okay, thanks. And so, I mean, if I can just add quickly on the cash management, it looks like you've drawn down about 50% or 60% of the ATM filing that you had done earlier in the year. Could you just comment on the timing of that with respect to obviously a growing set of clinical catalyst for the pipeline and the need to do that now versus down the road, especially, given a good cash balance already? Thanks.

Sure. So we are obviously pretty well-capitalized right now. And we – as we said, we believe, we have sufficient funding already to move all our late-stage programs through filings and launches. The total size of the ATM instrument is pretty modest relative to our market cap and trading volume. So the total filing was $450 million in gross proceeds and we’ve raised in that proceeds for approximately $59.7 million. Going forward, we may continue to use the ATM opportunistically from time to time in a pretty measured way, but there is no guarantee that we would use at all. And basically, our approach will be pretty opportunistic in the total size of it, again, it’s quite modest. As you know, the markets have been very volatile. And so the stock price has been declining even at times when we got positive news. And so we've just been opportunistically raising small amounts of capital to increase our flexibility.

Great. Thanks a lot.

Thank you. And our next question comes from the line of Edward Nash from SunTrust. Your line is open.

Hi, this is Mike on for Edward. Thanks for taking the questions. So a couple of quick question regarding our start program for MPS-7. The recent met with FDA and EMA just wants to get your some kind of feedback from the FDA, especially on the functional measurement?

So would you want the feedback from the FDA on the clinical data that we are going to submit?

Yes, please?

Yes, we reviewed the data with them and their conclusion with the data were sufficient to submit in a filing. However, they were not really able at this time as to leave question whether they believe we've shown enough efficacy or not. But they felt there was enough data to provide a filing and we work to talk about how to present that data for their most optimal review. And they disappoint once file and they’ll look at the clinical data overall as a review question. I think it was important to be able to get to a filing as a first step, so that we can talk through the efficacy. We think the urinary GAG data will show profound and effective just the FDA has not yet accepted that as a primary endpoint, as we’ve talked before. And so they'll look at each patient on a case-by-case basis and make that call, but they want to do that in the filing during review rather than in a pre-BLA meeting. So we won't have that that insight yet. But personally, I think, being able to file puts us in a position to advocate for these patients and we think we've done a sound job which we can in a very small population of patients. So we think we’re in reasonable place to move forward with the agency and continue discussions after a filing.

Got it. Thanks or a additional work you need to do before filing for example [indiscernible]?

There’s no additional work we have to do we're just getting putting the other filing you may have noticed that we are redoing KRN23 filing for Europe in December. In addition we’re prosecuting 01 so we’re doing a lot of major filing work right now and so the filings is in March partly to help manage the flow of major filing globally.

Got it. The last question for me is about first product is as we know ultra-orphan indication just want to get your thought at the patient identification program the common in patients have you identified so far if you can share. Thank you.

Yes, I know I think it’s important we have a global patient identification program although I think we haven't gone very deep in the South America yet we are starting to build our effort with a basic commercial group just coming together in Europe and in the U.S. we have standard our patient diagnostically is on the particular people focused on diagnosis. So we’re currently driving that ahead and we keep patients one by one in the sign of indication showing up. We haven’t yet put out the current numbers and at some point we get close to launch we’ll talk about where we are regard to the patient ID program, but we’re not really disclosing that at this point in time, but it is important effort for us not just for MPS7 for all our program and we put a lot of effort into it. Now not just U.S. but both Europe and South America as well.

Okay. Thank you.

Thank you. And our next question comes from the line of Carol Werther from H.C. Wainwright. Your line is open.

Thank you for taking the question. So just to clarify with KRN23, if the adult data is positive, it will be included in the submissions and therefore, might be in the label, even though, the breakthrough designation is for pede?

Well, that is our discussion with the agency is that the adult data – would that be sufficient for getting the label. We think that that should be that the Phase 3 study. It may not be part of the breakthrough, but and the adult would tag along with the Phase 2 data in that regard. We haven't really settled down what we're doing for the filing. As I said, we have to talk in the pre-BLA meeting.

Okay.

But the ability to file with Phase 2 and plus the adult Phase 3 is certainly one of the options that we could go forward with. And that's what we have to discuss what's the fastest way forward to get the broadest label, right, Carol, that’s kind of a – it’s a good point, and we need to understand how that is and what to do. And so, would be one option we will file with both of those and some other under five data and potentially get us there. But until we have the pre-BLA meeting, we can't really to give you a very precise picture of what the outcome will be. And we don't want to commit to something that we don't have firm discussions with the agency of the world and giving the updates that pediatric Phase 3 would not be required before we could file peds. So I think that that is an important change. And at that this point, we’ll have to get a little more deep into the discussion as to verify what we can file? When and what our proposal would will would be for the label.

And then just lastly, I just wanted to ask business development question about, basically you’re still looking for other products in-licensed and/or are you on schedule with your planned INDs? Thanks.

So we are always looking for product. But we have – well, I can say practice on adults this will probably our next IND when that happens and we're pretty full up in our clinical development right now with on nearly 30 clinical studies ongoing and half-a-dozen or more very speed studies. So we're in a very busy place on the clinical side right now. In the IND, once we clear some of these filings, I think we can think about INDs and some other programs. There’s the Takeda programs, we’re working on, as well as some other things in early stage. We don't really like to talk about our earlier stage stuff, it’s heading to IND, because we don't want to make promises to either investors or to patients about what's going to happen. But we are committed to getting to the IND every year, every other year pace. So we can reach a steady state of four to six months of stage programs and hopefully hit filings every year or every other year for approval as a steady state. That is our target.

Thanks so much and congrats on the progress.

Sure. Thank you. And at this time, I’m showing no further questions. I would like to turn the call back over to Mr. Ryan Martins, Vice President of Strategy and IR for closing remarks.

Thanks, Amanda. This concludes our call. A replay of the call will be shortly. If there are any additional questions, please contact us at 8447587273 or IR@ultragenyx.com. Thanks, everyone.

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect. Have a great day.