Ryan Martins - Vice President of Corporate Strategy and Investor Relations Emil Kakkis - President, Chief Executive Officer, Director Shalini Sharp - Senior Vice President, Chief Financial Officer.

Adam Walsh - Stifel Dae Gon Ha - Leerink Partners Laura Chico - Raymond James Arlinda Lee - Canaccord Liisa Bayko - JMP Securities Vincent Chen - Bernstein Research Cyrus Amoozegar - Morgan Stanley.

Good day ladies and gentlemen and thank you for standing by. Welcome to the Second Quarter 2017 Financial Results Conference. At this time, all participants are in a listen-only mode to prevent background noise. [Operator Instructions] We will have a question-and-answer session later and the instructions will be given at that time.

Now I will like to welcome and turn the call to the Vice President of Strategy and Investor Relations, Mr. Ryan Martins..

Thank you, good afternoon and welcome to the Ultragenyx Pharmaceutical financial results and corporate update conference call for the second quarter of 2017. 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, our Chief Executive Officer and President; and Shalini Sharp, our Chief Financial Officer.

I would like to remind investors that this call will include forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as forward-looking in our quarterly report on Form 10-Q filed on May 5, 2017, quarterly report on Form 10-Q for the quarter ended June 30, 2017 that will be filed soon and our subsequent periodic reports filed with the SEC which will all be available on our website in the Investors section.

These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statements.

For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks relating to our business, see our periodic reports filed with the SEC. I will now turn the call over to Emil..

Thanks Ryan and good afternoon everyone and thank you for joining us. I will be start by discussing our recent progress and milestones, Shalini will then give an overview of our second quarter results.

We continue to make regulatory progress during the quarter with two of our clinical programs, Burosumab for XLH and Vestronidase alpha or rhGUS for MPS7. For Burosumab we have had a productive pre BLA meeting on the clinical package with the FDA. As a result, we are planning to submit the BLA in the U.S.

for treatment of adult and pediatric patients next month. And out today Burosumab results from two patients in the Burosumab along with statistical analysis of bone fracture healing in the phase 3 placebo-controlled study both of which will be included in the filing.

At the pre BLA meeting the FDA agreed that the BLA could be submitted based on available clinical data and confirmed that both pediatric and adult indications would be included in the review.

Additionally, we have to confirm that the data from the ongoing pediatric phase 3 study would not be required and agreed to accept any available bone biopsy data from the 40-week open label bone quality study in adults as support of evidence. So today we announced two new pieces of data in adult patients that will be included in the Burosumab filing.

First bone biopsy results from the first two patients from the bone study will be included in this filing. In this study adults, base line biopsies were obtained from 11 patients.

The baseline data confirmed that the majority of the patients have severe osteomalacia with a mean osteoid volume ratio to bone volume of 26% versus the normal range of 0.3% to 3.1%. These data verify that adult XLH patients have severe underlying bone disease even many years past puberty.

Follow-up biopsies after 48 weeks of burosumab treatment are available from the first two patients. For these two patients, osteoid volume to bone volume ratio was decreased from 24% and 29% to 9% and 7%, respectively. The Osteomalacia was characterized by the pathologist [indiscernible] is improving from severe to mild assimilation in these patients.

These initial data provide important supportive information on the treatment of the underlying bone disease assimilation present in adult XLH patient which can lead to the facture of the observed need patients. We also planned to include a new post-hoc statistical analysis from the adult phase 3, placebo controlled study on fracture healing.

This now shows an odds ratio of 7.76 for complete healing of fractures and pseudo fractures in the burosumab treated group compared to the placebo group for the Ps value is 0.0004 at 24 weeks.

Now pushing the view of our conditional MAA for burosumab in Europe our partners KHK and KK have decided to separate the adult and PH indication to avoid any potential delays in the review procedure to the large amount of recent data from the adult XLH phase 3 study that we planned to file.

There was a conditional marking observation focused on the pediatric indication and KHK and KKI will submit for adult after a decision is first reached on the pediatric indication. An additional developments of burosumab, burosumab for the treatment of XLH has also now been designated the drug for a rare pediatric disease by the FDA.

If we receive approval for burosumab on XLH we would expect to receive a voucher for a Priority Review of a subsequent marketing application for a different product. We would likely sell any Priority Review Voucher to a third party. If the PRD were to be sold, we’ll split proceeds 50-50 with KHK.

A couple of months ago, we signed agreement with a wholly-owned subsidiary of Kyowa Kirin, which grants us the right to commercialize burosumab in Turkey. They have the option to take over commercialization efforts after a certain minimum period. Now turning to Vestronidase alpha or rhGUS MPS 7.

We announced in May that the FDA and EMA had accepted BLA and MAA filings Vestronidase alpha was granted Priority Review Status from the FDA and the PDUFA date of November 16, 2017 and the CHMP opinion is expected in the first half of 2018. The review process with the FDA is moving on normally.

We do not expect the advisory committee meeting at this time. So now I'll go through some upcoming milestone future programs starting with burosumab. We are planning to file US BLA for burosumab in adult and pediatric patients in August of 2017. In Europe, we are expecting the opinion from the CHMP around the end of 2017.

In late 2017, early 2018, we will expect for complete data from the bone quality study in adults with XLH. Now moving on to Vestronidase alpha. Vestronidase alpha has PDUFA goal date of November 16th and CHMP opinion is expected in the first half of 2018.

For UX007, we are evaluating potential for an event based UX007 in Glut1 patients with absence seizures and we will update you as we move more. The things we study in Glut1 patients ongoing achieved plan or discussions regulator regarding the Phase 3 study in patients with FAOD.

Lastly for Ace-ER, we expect data from the pivotal Phase 3 study in GNE myopathy in the second half of this year. The fully enrolled, double-blind, placebo-controlled international study evaluates the efficacy and safety of the Ace-ER compared with placebo over 48 weeks in 89 patients. If these data are positive, we plan to submit an NDA and an MAA.

With that, I will turn the call over to 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 second quarter of 2017 was $72.9 million or $1.72 per share basic and diluted compared with $56.9 million or $1.46 per share basic and diluted for the second quarter of 2016.

This reflected cash used in operations of $110 million for the first six months of 2017 compared with $84.6 million for the same time period in 2016. We continue to expect cash used in operations to increase moderately throughout the year.

Net loss for the first six months 2017 included approximately $30 million in non-cash charges including stock-based compensation of $31.3 million, amortization of premiums on purchased investments, depreciation and amortization and other non-cash charges offset by a non-cash inter-company foreign exchange re-measurement gain of $4.6 million.

We expect stock compensation expenses to continue to increase over time. Our total operating expenses were $78.4 million for the first quarter of 2017. Research and development costs were $58.4 million during this period -- during the second quarter of 2017, with our Phase 3 programs accounting for the greatest portion of R&D costs.

Costs on our multiple preclinical translational research programs were also increasing as programs advanced towards the clinic.

We expect the OpEx to increase during the remainder of the year 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, stage investments in our U.S., 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.

While our expenses will continue to increase significantly in 2017 as a result of these activities the rate of increase year-over-year is expected to begin slowing down. We do expect OpEx to increase during 2018 due to anticipated launch activity for both burosumab and vestronidase alpha.

We ended the second quarter with $457.5 million in cash, cash equivalents and investments on the balance sheet. I would like to take this opportunity to turn our attention to burosumab and review the terms of our collaboration with [KHK]. The agreements refer to three territories, the U.S. and Canada, Latin America and Europe. In the U.S.

and Canada for the first five years post launch Ultragenyx will launch burosumab and share development and commercial costs 50-50 with KHK. Ultragenyx will also pay KHK a supply price that is a significant fixed double-digit percentage of net sale.

This supply price was flat, higher than typical cost of goods margin for a biologic and essentially compensates our partner for the fact that we were not required to pay any upfront or milestones payments nor have we paid for the cost of product during the [indiscernible] period or any associated manufacturing costs.

After the first five years KHK will take over the majority of commercialization efforts in the U.S. and Canada and instead of the profit share mechanism Ultragenyx will receive a tiered royalty in the mid to high 20% range. This royalty is intended to reflect the same economics as during the profit share period.

Throughout this period the agreement states that KHK will book sales for burosumab in the U.S. and Canada. Turning to Latin America, the agreement states that Ultragenyx will commercialize burosumab and recognize revenue while paying KHK a low single-digit royalty on net sales.

In Latin America Ultragenyx will pay KHK the same supply price as in the U.S. and Canada, a significant fixed double-digit percentage of net sales. In Europe KHK will commercialize and book burosumab sales while Ultragenyx will receive a royalty of up to 10% of net sales.

As a reminder in Europe it can take 12 to 24 months for approved products to receive reimbursement on a country-by-country basis. Overall, we estimate that we hold roughly one third of the value of burosumab in the territories that are subject to the agreement. This concludes my remarks for today. And with that I will now turn the call back to Emil..

Thank you, Shalini. We've made tremendous progress on the regulatory front this quarter with the recent [indiscernible] for burosumab, near term plans to file for burosumab approval in adults and pediatric patients in the U.S. and acceptance of our vestronidase alpha BLA and MAA filings. Two products filed in the U.S.

and Europe within the years important accomplishment for the company. And this year we will also continue our preparation of global commercialization and I look forward to updating you throughout the year on our progress. Let's move to your questions at this time. Operator can you please provide the instructions for the Q&A portion of the call..

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

Maybe for Shalini while we're on the commercial worldwide rights to burosumab, can you just talk about whether we should think of Turkey maybe as like a Latin American type of territory and discuss your strategy and interest in acquiring rights at least for the near term there..

Thanks Eric, Turkey is actually a little bit different from all the other territories in agreement and since it's just a single country and not a material agreement for us, we haven’t disclosed a lot of the details around it. We do have a supply price type arrangement during the time that we are selling the products.

We do have to pay royalties during the time that we sell the product. And then there is a certain period after which was triggered by the approval in Turkey a certain period after which KHK has the option to opt into that country. And if that were to take place there are royalties to us in that scenario.

And obviously we would no longer pay the supply price. So, it’s a little bit complicated but again it's just a single country so we have opted it not to provide all those details..

Maybe a quick one for Emil on the bone biopsy data for burosumab again do you have all you need to file with the two patients or do you need a few more to get that submission in August. Thanks..

No, we have all we need to file, so they weren’t expecting NA actually to be in the filing they just thought during the review that if we could any biopsy we could get them they would like to them. So, we did have two and obviously the results were we think profound and show that these patients have severe osteomalacia.

So, I think that’s enough to tell them that burosumab having a fundamental effect on bone.

And as we collect some additional during the middle of the review there is periods of time where we will send in safety update, answer questions et cetera and we would expect to have opportunities provide some additional but I think having two in the filing we stay very close these patients have severe osteomalacia and the two that have reached 48 weeks were able to show an important impact on that osteomalacia..

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

Emil can you just update us on your thoughts on the potential for an adcom for burosumab and then also perhaps update us on the XLH patient identification efforts?.

Sure, now we have said for Vestronidase that are not -- we were not expecting an adcom. For Burosumab being a new molecule entity and mechanization, we would normally expect that would be wise mainly based on the FDA policy. We haven’t been informed yet of that. but I assume after we file we will find out.

But at this point we are expecting it but because it has been FDA policy. So, on patient identification we haven’t put an update on that. We are looking at patient application both U.S. and South America we now have people on the ground doing that and have implemented a larger team now in the U.S.

of 30 patients, I know [indiscernible] are actually covering 30 characterized and doing through a number of the identified targets are actually working to identify valid data physician to have patents. So, we expect that effort to help generate a solid lease for our launch assuming we get approved.

At this point we haven’t released the details on the numbers but we have put out before based on our ICE END at 9 and 10 code analysis that the 12,000 numbers it’s a reasonably accurate number for the problems of patients in the US and we don’t have any basis to change that number at this point in time..

Hey that’s still helpful. And then just one follow-up here. You mentioned that burosumab was designated as the drug for rare pediatric disease with the potential for pediatric voucher.

Is it possible that rhGUS for MPS 7 could receive the same designation and potentially also receive a pediatric voucher?.

Yes, well we have applied for the voucher for that program in the filing. So, we would expect that since enzyme got a voucher that’s certainly Vestronidase alpha would qualify for a voucher. So that will give us one voucher and one another, one and a half I guess if you count the half of the other one.

One advance you are getting product, so we got to get them approved first..

Thank you. And our next question comes from the line of Cory Kasimov with JP Morgan. Your line is open..

Hi, this is Brittney in for Cory. Thanks for taking the questions.

And your pre-BLA discussions with the FDA for burosumab, has anything changed at all regarding the importance of hitting all three key secondary endpoints? And then just a quick financial question, can you remind us of any milestones that are owed to Baylor Research either this year or next? Thank you..

Great. So, for the endpoints in our pre-BLA discussions, there was no actual concern or question raised on the p values or the secondary endpoint choices. They just want to know that we had validated those endpoints and they were fine with the results.

They did not tell us that we hadn’t hit something and that was an issue which would be rather unusual frankly that you never don’t have to hit all endpoints in any clinical study, plus all the trends on the ones that are very close, we are in the right direction. So, we don’t see any issue there based on that discussion at the pre-BLA meeting.

With regard to Baylor milestones, I don’t think we've normally done, Shalini would you like to take that one?.

Sure, thanks Emil. So, Brittney for the Baylor agreement the maximum milestone outlay that we might have over the next year would be in the low to mid six-digit range. Nothing very material..

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

Hi guys. Thanks for taking my question. This is Dae Gon Ha dialing in for Joe. Two quick ones Emil.

With regards to burosumab MAA, the decision to split the indication between pediatric and adult, I was wondering where there any particular questions or concerns at the KHK or EMA guys raised that kind of led to this discussion or was this purely on the substantial data package size? And second, can you also provide a little more context behind the bone biopsy data you provided today, the 24% and 29% breaking to mild [ph] pharma’s 9% and 7%.

What kind of quality of life difference can you expect on a patient who has severe to mild osteomalacia? Thanks..

Sure. So, for the ped adults' situation, the EMA had only seen the pediatric Phase 2 and the small adult Phase 2 in the actual package. And so, they have not seen the adult Phase 3 data, the fracture data or any of the other data.

So, it’s merely decision by our partners that they will concern the procedure might get bogged down by having too much additional data which might delay the procedure and sorted [ph] by narrowing it to the ped indication which was the one that for which the driver for conditional marketing authorization to begin with would assure they could move more quickly.

So, that was their decision, not our decision, they made that decision but it wasn't really based on -- and it was no EMA feedback on the adult Phase 3 in that decision.

Alright, so the question on bone osteomalacia, and what percent osteomalacia people feel? I haven't seen any one correlate precise exact amounts of osteomalacia but we have figured osteomalacia means your bones are very weak and fragile which means you'll have a lot of fractures.

Now when you look at the patients in the bone quality study, look at their age and type, we compare them to the Phase 3 study, they're actually very similar to what the patients in the Phase 3 study almost the same.

So, what I would say to you is that if you looked at the Phase 3 study, you have fractures, and significant impairment and what we're saying is they are in a very parallel similar population that was associated with the mid 20% osteoid in their bone, so we think that when you think clinically in terms of symptoms and benefits in that study are probably parallel to what we're seeing in the bone study.

But going from severe osteomalacia which is for patients who've been sick for 40 years or 40 years old on average to mild and just one-year period, I think is a very profound change in bone biology and so we'd expect that to translate into fewer fractures and better fracture healing and which should improve the quality life of patients.

Osteomalacia in general or excess osteoid does create a faint ache and pain in the bones which we'd expect to get better; the pain is complicated in this disease because there're other sources of pain, so controlling exactly would overall pain is tricky when you're looking at these disease in in advanced stage.

So, we think that change from several to mild osteomalacia will be an important clinical benefit to patients and it'll translate into things like fracture and pain and other symptoms over long haul. .

And Emil just quickly are you -- do you plan on providing the full 11 patient data at some point before the end of the year?.

Well our expectations that we'll catch -- because there was enrollment over a period of time, it will another group of patients' data during the middle of review that we should get to the FDA, they had asked us to get the data as it move on. It is not an essential piece it's just a supportive piece.

So, we would get some additional data based on the filing plan and what we'd expect would be a [indiscernible] PDUFA date, we would have all 11 data prior to expected PDUFA date. So, in a sense the FDA could see all the data before the actual decision is finalized..

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

Good afternoon guys, this is Laura Chico on for Chris Raymond today. Thank you very much for taking the question.

I guess I have two kinds of related to earlier questions that were asked, first on the rare pediatric disease designation for burosumab, was this expected just given the prevalence of the adult form or I guess number of patients with adult -- who are adults with the disease and then separately how should we be thinking about pricing in Europe now I guess that your kind of separating the pediatric and the adult designations or indications? Is there any change to thoughts on how that will be approached?.

Sure, so let me start with your first question, I'll let Shalini answer the second one. So, on the rare PS designation I think what you should understand about XLH is all the adults where symptomatic and sicker children.

So, the diseases of pediatric onset diseases all of them had sickness it's not like an adult onset disease, its only adult not children. I think that is the factor in understanding the disease. The fact that people don’t die shouldn’t prevent this from counting as a disease right.

That is the fact that there are people who survived childhood and lived to older age shouldn’t decrease this fact that this is a pediatric onset disease.

So, we filed it just to make it clear because if that question you raised and they’ve designated it such that it is a pediatric disease in that sense then have ruled on the question of whether the problem to adult matters or not or I think what they were basing this on was the fact that it is a pediatric onset disease.

And particularly pediatric record part of disease is profound too so I think that’s a problem plays into that decision.

So, pricing?.

So just talking about pricing on KRN23, so first of all there is no final price decided upon for KRN23 in any territory at this point. In terms of Europe itself KHK obviously is the driver of decision making on pricing in Europe.

However, we do work together in a joint commercial committee to develop a global pricing band within which we would agree to keep our net sales price within that range. Now on all territories I think everyone agrees that the pediatric population is the more acute population where the unmet need is most obvious.

And so that may play have some impact on pricing. But at the end of the day again no decisions have been made on that and essentially the adult population would also be hopefully submitted and approved in Europe.

Another data point on pricing is just if you just look at all of your colleagues on the cell side, there appears to be a cluster among the analyst around $100,000 to $125,000 per patient per year in terms of average annual patient price. Now one thing to note specifically for KRN23 is the dosing is little bit different between Ps and adult.

So, the pediatric patients are treated every other week and the adults are treated every month. And so, the pediatric patients receive almost double the dose per keg as adult so that provides a little bit of equalization across the age groups between Ps and adults.

So hopefully that gives you some guidance in terms of how to think about it but again we have made no final decisions on pricing..

And our next question is from the line of Arlinda Lee with Canaccord. Your line is now open..

Can you maybe go back and talk about the KHK breakdown of how the profit share work? What happens I guess in the ramp up to sales force? Are you in control of that in the share territories? Are they in control of that? And what happens to those sales force after year five? And then on the biopsy data, do you have any fractured data on those two patients? And will you be collecting that on the remaining nine patients? And then lastly, I'm sure I have to know and can you maybe talk about the timing of the FDA discussions on [indiscernible] that data I thought was available by the end of last year, what are kind of speaking points or the bottleneck and can you provide -- lastly can you provide an update on the Huntington's program in France? Thanks..

I’ll let Shalini deal with the profit share question first..

Sure. So, the only profit sharing territory Arlinda is the US and Canada. And in that territory, we share development and commercial costs 50-50 with KHK. We do obviously have a joint commercial committee where we coordinate on tactics and resourcing, strategy, market research, many things.

But ultimately in the US, we are the lead commercialization party right now and up until the time that KHK will take over the majority of promotional activities. The sales force has not addressed any agreement. So, we are building up a sales force to sell in market KRN23 in the US.

Currently, eventually in Canada over time our plan would be live that sales force across the other programs that are in our portfolio and we do expect there to be some overlap in terms of some veterinarian physicians across our multiple program. So, we expect to get some leverage out of that sales organization that we are building up.

Hopefully that answers your question. .

Yes, thank you very much..

So, on the second question; it’s fractured on two biopsies. We haven’t followed the fractured on two biopsies in those patients. We didn’t follow the fractured, follow the x-rays and other things. But the patients in that study are very comparable ones when we are monitoring fractures.

So, I think that I would say that we would expect osteomalacia improvement in fractures to be parallel biological processes.

Relative to FAOD, we did get the daily at the end of last year, but became initiated kind of a change in thinking originally been planning to do the exercise induced approach, it’s a tone [ph] approach and we now have shifted doing the event based strategy, at least we believe so.

And it takes a little time just to figure out for sure how many patients we can roll and what the strategy and design would be in order to talk to the FDA. We have submitted some things and seeing we are working through that.

That will take a little time I agree but we are hoping to get that resolved here in the second half and get something up and running. For mind disease, we don’t have any updates than that it’s an IST. We hear they are continuing to enroll patients but we have seen, we haven’t -- don’t know when they are going to finish the study and done report data. .

Thank you. And our next question comes from the line of Liisa Bayko with JMP Securities. Your line is open..

Hi, thanks for taking the question. Just to follow up a little more on the pricing question.

Is that something that you decide given that you kind of ultimately will beginning royalty but you will be kind of doing upfront commercialization in US and Canada, so in those territories, is that your purview to decide, or is there some joint decision? And to that point about kind of people being around between 100 and 125 can you give us some benchmark that would good, benchmarks for this kind of therapy [ph] that would be really helpful? Thank you..

So Shalini I think you should handle this..

Okay, thank you. Well to answer the second part of the question first, I don’t think we have very strong benchmarks for this therapy. I think the data has been quite striking to-date and I think that’s a helpful fact in terms of value creation for patients.

I think there are other rare bone diseases with approved drugs but they are pretty different from XLH.

So, I don’t think you can draw analogy, so for example some have asked us about [indiscernible], but that disease we're talking about enzyme replacement therapy, we're talking about a lethal infantile form so, it's not really exactly comparable in terms of XLH.

So, there's not a great comp out there, so far now I think the best thing we can do is point you to the cell side and again point out that we haven't made a final decision about pricing.

In terms of how pricing decision making actually works, so it is a very collaborative type arrangement that we do have a join commercial committee and that committee jointly conducts market research and again makes decisions about a global pricing ban regarding the net price of the product globally, so globally we would expect to be -- pricing for the product to remain within that band.

In each territory there is a defined sort of a lead commercial party, and in the U.S.

and Canada for the first five years post launch Ultragenyx is the lead commercial party in Europe KHK is always a lead commercial party, in Latin America we're obviously the lead commercial party, so that's how it works, there is a lead party, but there's a lot of coordination and discussion among the two teams, in the form of a joint commercial committee, there's a joint steering committee, there're escalation methods that are typical for collaboration and [indiscernible] agreements, so nothing too unusual there, so it's a lot of coordination but also some lead parties defined..

Thank you. And our next question is from the line of Vincent Chen with Bernstein Research. Your line is open..

As you approach the completion of the burosumab BLA filing and approval looms on horizon, no doubt you've had fairly extensive discussions with payers who will try to grease the [indiscernible] for a robust launch, how are you fishing the pharmacoeconomic argument for both the pediatric and adult populations relative to current therapy, is there an ability to differently price the drugs who reflects greater value in the pediatric imitation [ph].

And what are you hearing from payers with respect to how pricing might affect the level and type of restrictions applied, whether that's pre-authorization criteria that are being contemplated or criteria for reauthorization?.

Well we can talk about the case for burosumab, we wouldn't really discuss ongoing payer discussions, I think that there's a lot more to be done before we get to the launch stage on that and pricing.

I think when you look at the -- the pitch we certainly would make is based on the data we have and looking at the [indiscernible] studies the patients even on existing standard of care are severely disabled. Essentially all the patients have a [indiscernible] and are result in multiple surgeries and disability as older patients.

And the fact that of study shows these patients rickets are substantially improving, that their deformities are resolving, their growth is improving, their pain and physical function in the pediatric patients are improving and in adults the fractures are healing as well as improvements in bone remodeling function.

We think that treatment really has no comparable, the oral [indiscernible] standard of care is a very modest drug but it also has substantial clinical side effects and particularly around 25% to 30% of the patients have nephrocalcinosis or basically calcification of kidneys which in many cases leads to kidney stones, in the old days when you try to use even more of that treatment to get better, [indiscernible] 50% to 100% of the patients have calcium in their kidneys, so we think that from a safety perspective that for us it will substantially safer in how it works particularly.

If you take the combination of the effect on rickets, and deformities and growth and fractures and procedures and look at that over the long haul we think that'll be a substantial case for changing what is a very disabling disease into one that’s manageable.

I know we need to work on that argument and develop the case and the team in our groups will be doing that continuously going forward..

And with the adult XLH population, a much larger portion of this whole patient pool and one way of treatment is currently fairly and frequently and very and unevenly applied. What steps are you taking to really drive [indiscernible] and the eventual adoption.

It seems as though in our discussions that many of the key opinion leaders in the XLH phase believe there's true benefit to treatment in adults. But really the secondary group of physicians managing XLH appear to treat adults fairly and frequently.

I guess what's your sense for a portion of patients who are managed by the XLH thought leaders rather than the broader secondary group.

And also, what are you doing to ensure adults who can benefit indeed get treated whether it’s a matter of educating the broader physician community or driving adults for the XLH specialist centers?.

Well with regard to treatment of adults, whether its [indiscernible] or other centers, the biggest issue has generally the thing that’s been limiting is the fear that they are going to damage our kidneys and so a lot of doctors won't do it with fear of damaging the kidneys of an adult patient just from the essentially the risk standpoint.

And therefore, there are certain doctors just treating no one because of the risk issue completely.

The other doctors that are doing the treatment whether keeping the other are treating around half the patients and that’s based on the number of patients that have severe enough bone disease that they are willing to take the risk on the kidney injury question.

And so, when we look at this I think there are going to be different opinions and different amounts of awareness but everything we've had if you look at patients and talk to them directly with adults there is severe disability and dysfunction those patients and that hasn’t been well appreciated, we'll be and it's one of our job to make the physicians aware of it.

most of them though I would say are afraid to treat because of the damage of the patient and discomfort with the current therapy..

What's the plan for how you drive that awareness?.

Well we are doing currently is our patient diagnostics will teams will talk about disease out there with doctors and adults and we are working closely with the patient advocacy group and making them aware and they are actually rather shocked at how the adult of these are under appreciate.

I can tell you when I have hold them that as they have been very surprised that they aren’t appreciated how the stable they are.

So, we are working with patient advocacy and our patient diagnosis is on the field, we look to raise awareness on the disease burden and the serious issues that exist with adults and work with our patient advocacy colleagues to help raise awareness among the patient communities that XLH adult disease is not my hold, it’s a severe disease.

We think actually the data from the biopsy study will allow us to show that the underlying disease in these patients is severe and even if unrecognized in some areas.

We are pretty confident that combination of disease awareness efforts to our patient [indiscernible] with advocacy efforts in addition of the support of its clinical data will be enough to start this.

The other thing I'll tell you that I think is extremely important for piece of the recognized is that adult issues are not [Technical Difficulty] pediatric patients are not separate groups, they are not living separately. All the pediatric kids have parents and most of those parents have XLH too.

So, when you are treating a pediatric patient in the same household, the result with XLH and there will be ends with XLH or [indiscernible] with XLH so you start treating kids and they get better, their awareness will go throughout the family tree.

And it won't be like two separate populations for two separate doctors because the families are all in one group. So, think of it less about what the doctor and think about the underlying family. If you look at other [indiscernible] disease like [indiscernible] that has been quite instrumental in the launch is the connections of the family trees.

So that one person getting treated getting a result now translates into interest from other family members..

How concentrated in the treating population?.

Well, we recently did an analysis which we had in our investor deck and there’s actually quite a few physicians across US, there are appear to be treating hypophosphatemia patients with or prescribing phosphate. So, they are fair number.

We know that the major ones are in the pediatric endocrine nephrology area but we are seeing some other doctors in medical genetics and orthopedics and some other centers that are actually treating patients.

So that data though because they are prescribing a drug the oral phosphate can be tracked, it allows us to find all those people and with our patients' diagnosis is on team to be able to go out and contact and validate which are those doctors actually are treating XLH patients and to help focus our efforts on those physicians that we know have patients.

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That must be a pretty long tail to those, how many you were able to catch with the efforts you’ve put out there so far?.

Well, we haven’t talked about the exact number but we have hundreds of patients in our various centers that we have already seen and a lot of centers have many, many patients.

So, I personally was a doctor and I had a lot of XLH patients in my clinic, that’s why we are working on it because I was thinking about I have so many of these patients and I was thinking there must be some better than the therapy I was prescribing which was a phosphate. So, there are a lot of the centers have quite a few patients.

So, it’s not like NPS disease where you are dealing with one or two at a time..

Thank you. And our next question is from the line of Matthew Harrison with Morgan Stanley. Your line is open..

Hi, yes. This is Cyrus on for Matt. Thanks for taking my question. A couple of things for KRN23.

So, for the bone biopsy data, how do you expect the FDA to treat that from the pre-BLA meetings, did it seem more like it was just helpful for maybe underlying mechanism or was there some sort of read through [ph] to efficacy and labeling? Also for the dual time line finally in the EU for ped in adults, what is the impact on your expectations for when each of these indications will be available to patients?.

Yes, so on the first question, bone biopsy question, I think they just wanted verification on the mechanism action. They considered that an important efficacy parameter by the way and the group there at FDA does deal with osteoporosis and other disorders where biopsies are using various ways to look at the biology.

Based upon confirmation that they are seeing a change in the underlying biology which we think we already shown in the first two, that is not just a change but a profound change in one year.

So, we think we have -- we can meet their interest which is showing the mechanism action in doing what we think it’s doing, which I think enhances your ability to understand why the fracture healing is happening.

It’s happening because the opioid is being changed and mineralized possibly to make strong bones that now can -- so that’s on the bone biopsy.

On the time of the filing, the timeline we are putting forth on the pediatric indication is the same as before and it will depend on KHK filing the adult indication after the decision on the peds indication and so that will initiate as a type two variation a follow-up filing in the timeline for review will be expected what the review is now, we'd expect..

Thank you. And our last question is from the line of Mario [indiscernible] with Jefferies. Your line is open..

I'm just wondering if you can remind me what we'll see for the GNE Myopathy results, potential form for that and if its positive would the NDA and MAA be filed by year end?.

So, GNE Myopathy study just to remind everyone, the 89-patient randomized double blind placebo controlled, and the primary endpoint is the upper extremity composite of muscle strength -- core muscles measured and that's the primary -- that’s the end point released in the Phase 2 study.

Secondary end points include a couple muscle strength measures of the lower extremity and a GNE [indiscernible] or functional activity scale as well, and so we're -- we only need to show an effect in the upper extremity to be able to file and getting the effect in lower extremity would be beneficial but not required, so we're looking to see a support statistical significant result based on the powering we would think that result would be -- we would be comfortable what we've seen before and therefore things that would be sufficient to file.

Our timeline for filing is probably in early '18, probably wouldn't make it by the end of the year. That would be a very short period of time and honestly, we're also prosecuting two other filings simultaneously right now. So, I would expect that filing in the first half of '18..

And just quickly on the post-hoc bone fracture stats, I was just curious if that was possible to [indiscernible] statistically at 12 weeks, and then potentially breaking out the complete versus zero fractures?.

We did look at it, it is also positive at 12 weeks, it's more positive at 24 weeks.

I can't recall -- we have broken out, but we don't -- we've said before that we didn't see a difference in the fracture changes for pseudo or full fractures, they both improve similar -- through a similar ratio, that makes sense, so it's not only like there is one or the other are moving the numbers or both moving..

As far as the stats at 12 weeks that….

Yes, it was also happening, it was positive, at 12 weeks, but I think it doesn't -- it's so strong at 24 weeks and the odd ratio of 7.76 is a math of odds ratio, I am not sure how familiar you're with the odds ratio, that’s a huge number, so, it just shows that the treatment effect size is quite profound in terms of the healing of fractures..

Thank you. And with that we conclude our Q&A session for today. I will turn the call back to Ryan Martins for his final remarks..

Thank you, and with no additional questions, this concludes the call. Replay of the call will be available shortly. If there're any additional questions, call us at 844-758-7273 or ir@ultragenyx.com, thanks..

And thank you all for participating in today's conference. This concludes this program and you may all disconnect. Have a wonderful day..