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.

Eric Schmidt - Cowen and Company Brittany Terner - JPMorgan Adam Walsh - Stifel Laura Chico - Raymond James Dae Gon Ha - Leerink Partners Tazeen Ahmad - Bank of America Arlinda Lee - Canaccord Liisa Bayko - JMP Cyrus Amoozegar - Morgan Stanley Yigal Nochomovitz - Citigroup.

Good day ladies and gentlemen and thank you for standing by. Welcome to the Ultragenyx first quarter 2017 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].

I would now like to introduce your host for today's presentation, Mr. Ryan Martins. Sir, please begin..

Thanks Alan. Good afternoon and welcome to the Ultragenyx Pharmaceutical financial results and corporate update conference call for the first 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, VP of Strategy and IR.

With me today are Emil Kakkis, Chief Executive Officer and President and Shalini Sharp, our Chief Financial Officer.

I would like to remind investors that this presentation contains forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as identified as forward-looking in our 2016 annual report on Form 10-K filed on February 17, 2017, quarterly report on Form 10-Q for the quarter ended March 31, 2017 that will be filed soon and our subsequent periodic reports filed with the SEC which will all be available on our website at ultragenyx.com in the 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 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, please 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 start by discussing our recent progress and milestones and Shalini will then give an overview of our first quarter results. We started the year with promising data and significant advances for two of our read programs, burosumab or KRN23 and UX007.

In April, we announced positive 64 week data from the UX007 Phase 2 study of burosumab where the data shows that serum phosphorus levels, rickets, growth rates and functional outcomes improved with burosumab treatment. The same effects we saw at the 40 week time point in the study were maintained through 64 weeks of treatment.

Safety was acceptable with injection site reactions as the most common treatment related outcome which were generally mild. We believe these longer term data on safety and efficacy further support burosumab's impact on bone health and growth in children and are finally BLA filing in U.S. pending our pre-BLA meeting with the FDA.

In April, we announced interim 24 week data from a separate pediatric Phase 2 study in patients aged one to five years. In this study, patients demonstrated increases in mean serum phosphorus and maintained levels in the low normal range through 24 weeks of treatment.

Patients also demonstrated increases in serum 1,25-dihydroxyvitamin D levels and significant decreases in alkaline phosphate levels. Safety observed was comparable to that observed in the older five to 12 year olds study.

Last month, we also announced positive 24 week data from the randomized, double-blind, placebo-controlled Phase 3 study of burosumab in adults with XLH.

The study met its primary endpoint of increasing serum phosphorus levels and demonstrated a statistic significant improvement with stiffness after pre-specified multiplicity adjustment and strong trends in pain and physical functioning.

Burosumab has been well-tolerated in the study with a similar safety profile seen in the Phase 2 pediatric study in five to 12 year olds. Approximately 23% of patients had injection site reactions, all of which were considered mild.

Since the recent release of the adult Phase 3 data, we have had some additional positive data on the healing of fractures. We previously noted that the achievement of mean peak phosphate levels in the normal range and also a substantial increase in bone formation [indiscernible] in burosumab patients, but not in the placebo patients in the study.

The improved bone turnover and production would be expected to be associated with fracture healing. In our protocol, we have planned analyses of fracture healing in our additional endpoint, which are not part of topline results, but are now available.

Fractures were identified at baseline using a skeletal survey of all patients and those with fractures identified were followed with further X-ray evaluations at week 12 and week 24. The X-rays are scored by two radiologist and third adjudicator in a predefined blinded evaluation process.

They find 52% of patients, comprising 48% of KRN23 patients and 56% of patients on placebo present with either fractures or pseudofractures or both. At week 24, 37% of active fractures or pseudofractures in patients treated with burosumab were completely healed compared to 10% on placebo.

Additionally, at week 24, 3% of existing active fractures or active pseudofractures in patients treated with burosumab worsened compared to 11% worsened on placebo.

The changes observed with fracture healing are consistent with the impact that normalizing phosphate has on bone metabolism and likely the underlying osteomalacia that leads to fractures in these patients. Additional data from the study will be presented at a future medical meeting.

With burosumab, we have now reported positive data for patients in all age group studies including one to four, five to 12 and 18 to 65 year old subjects and have consistently shown that burosumab increases in serum phosphorus levels in these patients with all patients across the studies reaching the normal range.

Burosumab has also been shown to improve bone mineral metabolism increase bone biomarkers which is associated with improvements in the bone diseases, whether it is set by rickets growth or fracture healing. These improvements were associated with improvements in symptoms in both pediatric and adult patients.

The studies have also shown an acceptable safety profile for burosumab confirmed by the first placebo-controlled results in the adult Phase 3. We look forward to discussing the package of data along with the new fracture data with regulators. Now, switching to our UX007 program.

In March, we announced the data from the Phase 2 study of UX007 in Glut1 DS patients with seizures which showed a clear and substantial reduction in absence seizures which were considered clinical proof of concepts for the treatment of absence seizures.

The seven patients who only have absence seizures and completed both EEGs showed a mean 92% reduction in seizure frequency. Four of these patients had a 100% reduction from seizure rates of 7.9 to 331.5 per day, decreasing to a rate of zero seizures per day.

Safety was consistent with other studies and the most common AEs were mild to moderate GI events involving vomiting, diarrhea and abdominal pain and usually are managed with dose titration or administration with food.

Given these clinically significant reduction in absence seizures in Glut1 DS patients, we are evaluating potential plan to conduct a randomized control study to support the absence seizures indication based on these promising results.

It has been reported that about half of Glut1 DS patients with seizures have absence seizures which suggested that a treatment for absence seizures would be important to these patients. Last week, we announced that we initiated a Phase 3 study of UX007 for the treatment of Glut1 DS patients with disabling paroxysmal movement disorders.

This is global randomized, double-blind, controlled crossover study that evaluates the efficacy and safety of UX007 in approximately 40 patients. In previous investigator sponsored study of UX007, six patient showed that UX007 can reduce paroxysmal events by about 90%.

The events occurred on withdrawal of UX007 and then reduced again on reintroduction of the drug. Disabling motor events were about 70% of total motor events observed. About 30% of all events observed scored, disabling motor events were substantially reduced to a similar extent of the overall total movement events.

These disabling motor events are the primary endpoint of variable we will study in the Phase 3 study. I will now go through our upcoming milestones for each program, starting with burosumab.

We are on track on our plan to file a biologics license application for burosumab in the second half of 2017 based on the pediatric Phase 2 data and the adult Phase 3 data that we recently announced. We plan to discuss the details of the submission in a prevailing meeting with the FDA and we will provide an update after this meeting.

In Europe, our burosumab filing was challenged by the European Medicines Agency at the end of last year and we expect an opinion from CHMP by the end of 2017. In the second half of 2015, we expect additional 40 week treatment data from the Phase 2 study of burosumab in children between the ages of one and five years.

The 40 week data will include wrist evaluation by X-rays. In late 2017 or early 2018, we also expect data from the bone quality Phase 3 study in adults with XLH that is evaluating the resolution of osteomalacia based on bone biopsies and smaller and longer 40 week open label study.

These data could provide important support information on the treatment of underlying bone disease, osteomalacia present in XLH patient, which can lead to the fractures of these patients. Moving on to rhGUS. We are on track with regulatory filings in the U.S. and Europe in the first half of 2017 based on the positive Phase 3 data from last year.

For UX007, as I mentioned earlier, we are evaluating our options for UX007 in Glut1 DS patients with absence seizures and we will update you as we know more. We continue to plan for discussion with regulators 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 first quarter of 2017 was $68.3 million or $1.63 per share basic and diluted compared with $52.8 million or $1.25 per share basic and deluded for the first quarter of 2016.

This reflected cash used in operations of $61.2 million for the first three months of 2017 compared with $44.9 million for the same period in 2016. We continue to expect cash used in operations to increase for the remainder of the year.

Net loss for the first quarter of 2017 included approximately $15.6 million in non-cash charges with stock-based compensation of $14.5 million, amortization of premiums on purchased investments, depreciation and amortization and other non-cash charges. We expect stock compensation expenses to continue to increase over time.

Our total operating expenses were $70 million for the first quarter of 2017. Research and development cost were $51.3 million during this period with our Phase 3 programs accounting for the greatest proportion of R&D cost. As a reminder, we share burosumab development cost 50-50 with our collaborative partner Kyowa Hakko Kirin.

Costs for our multiple preclinical translational research programs are also increasing as programs advance toward the clinic.

While OpEx this quarter is relatively as flat compared with Q4 of 2016, due largely to timing of expenses, we expect it to increase during the remainder of the year due to the initiation of additional late stage clinical studies, manufacturing cost related to clinical supply of multiple programs, increased regulatory activity across the programs including filings for approval, staged investment 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 going forward. We ended the first quarter with $506.1 million in cash, cash equivalents and investments on the balance sheet.

We believe that we are in a position to fund all of our current clinical programs through Phase 3 trials and to potential launches and we do not have any debt outstanding. With that, I will turn the call back over to Emil..

Thank you Shalini. This year is off to a strong start with positive data from our burosumab studies in both pediatric and adult patients with XLH. We are planning to advance this program and our rhGUS program into the regulatory process here.

UX007 seizure data showed promising results in absence patients and we continue to evaluate options in absence seizures while simultaneously advancing this compound to the Phase 3 study in the Glut1 DS patients with movement disorders and also in fatty acid oxidation patients.

Finally, we expect Phase 3 data from the Ace-ER in GNE Myopathy program in the second half of this year. In summary, by the end of this year, we expect to have two programs with global regulatory filings, four active Phase 3 studies leading a robust clinical program in multiple translational research programs.

Our strong team continues to push these programs forward. We are preparing for potential near-term global commercialization. I look forward to updating you throughout the year on our progress. Let's move to your questions now.

Operator, can you please provide the instructions for the Q&A portion of the call?.

[Operator Instructions]. Our first question or comment comes from the line of Eric Schmidt from Cowen and Company. Your line is open..

Well, thanks for taking my question. Congrats on the progress. Emil, I assume that the bone healing data that you provided this afternoon was prespecified endpoint, but you are not allowed to give you a p-value because it was hierarchically determined.

Is that right?.

Well, it was considered one of the other endpoints in the study. So it wasn't part of the prespecified hypothesis testing. So we didn't do the analysis. We can do something post-hoc but because it wasn't among the core multiplicity adjusted endpoints, we didn't announce the p-value.

I think what you can see is, I am not really concerned about it because the ratio of change 37% to 10% is a pretty profound difference in healing. So we are comfortable on the meaningfulness of that. We can do some additional work and statistics. But we didn't release it because it wasn't part of the prespecified analyses.

However, I will point out that we did it in a rigorous way with blinded reading, et cetera. So I think it was done in a way that makes it a credible result..

Okay.

And then in terms of the pre-BLA meeting that you are looking forward to with burosumab, other than the usual sort of stuff, what does the FDA think of the data, can you file, et cetera? Or is there anything that you are looking to get back from the agency in that meeting?.

Well, obviously the first thing is confirmation that this is package data is ready for filing. The number one thing you get for a pre-BLA meeting. There are also a number of secondary technical details that are not worth discussing at this point in time.

But obviously we will talk about our proposal to file for pediatric and adults with this set of data. We will also give them an opportunity to tell us about things they want to see in the BLA.

We how to come out of the meeting with yes, we can file and we are filing, the intent to seek approval in pediatrics and adult and we will have whatever tech details worked out that would be important for the FDA in their review..

Thank you..

Thank you. Our next question or comment comes from the line of Cory Kasimov from JPMorgan. Your line is open..

Hi. It's actually Brittany, on for Cory. Thanks for taking the questions.

So just looking to later this year for GNE Myopathy readout, can you just help set expectations what you like to see, what would be considered clinically meaningful?.

Sure. So the study is, to remind everyone, has a composite of upper extremity strength as the primary endpoint and what we are looking for is a demonstrated statistic significant result, which we believe would happen with the range of something like, let's say 4% to 8% kind of range is where our expectation would be.

Because it is an international study, we have a larger effect, may be 8.5% to 4%, I would expect it to be little bit smaller than what we saw. What we know from the EMA and our discussions was the magnitude of effects seen in Phase 2 was sufficient in their mind.

We did not have to prove a larger effect with that size effect we have seen was sufficient. So we think it's in that range. Now proving clinical benefit, well, we hope to support it through the use of the GNE FAS scale, the functional activity scale, which is secondary endpoint.

The second endpoints though will also look at lower extremity strength and we look at the scores and the lower strength to help with that.

But our view right now is that if we get statistic significant stabilization in muscle strength compared with a decline in placebo that our understanding is that would be sufficient to show benefit, at least from the EMA standpoint..

Okay. Great. That's helpful. Thank you..

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

Hi. Thanks for taking my questions. My first one is on the MAA in Europe.

Will you be folding in the recent adult data into the MAA in Europe? And does that potentially extend the timelines for CHMP opinion?.

Yes.

Well, our expectation is to take all the -- we are filing our traditional marketing authorization and working closely with KKI which is a subsidiary of Kyowa Hakko Kirin who is going to be commercializing there on the planned for patients to submit the adult Phase 3 data, the complete Phase 2 peds data and the under five data, all that data will get submitted as answers to questions and the process.

Our expectation is it wouldn't but we want to make sure by discussing that with the regulators. But our expectation is that this data was expected. We had told them that was coming when we talked to them about filing the traditional marking authorization. So it should not be a surprise to them.

They knew that and they knew what the process would look like..

Terrific. And just one more, if I can. On the Fanny Mochel study in Huntington's, obviously it's investigator sponsored, do you happen to have any update there? And then would you consider initiating your own company sponsored Huntington's study? Thanks..

Well, as we have said in the past, it is an investigator study and it's up to her and their conduct. It is moving along, the study and we haven't set a timeline for releasing any information from the study. We are supporting the study though extensively and it is a 100 patient randomized study.

And our expectation is based on data from this study, we would decide whether we would initiate a Phase 3 or our own Phase 3 randomized study at the appropriate point in time. But we haven't discussed the timeline for that data yet. I know it is going along well and maybe something to happen later..

Thanks very much..

Thank you. Our next question or comment comes from the line of Chris Raymond from Raymond James. Your line is open..

Hi. Good afternoon. This is Laura Chico, on for Chris Raymond today. Congratulations on the progress. I guess, just one quick question on burosumab.

Bone healing data that you highlighted tonight, just curious if those trends they are kind of correlating at all by age or perhaps phosphate normalization? Or if you have done of analyses yet and which forum we might get to see the detailed data?.

Yes. Laura, we have just gotten the top line analysis of these other endpoints. So we don't have all these secondary analysis understand trends both age phosphate response to decide who is responding or who is not.

A good fraction of the total fraction are responding and it appears they are improving over time just as we saw on the endpoints or the progression over time. So I wouldn't necessarily look at that data to decide which fraction of patients can respond.

I would look at it more as evidence that adult patients have clinical problems that can improve by treatment. But the true sense of what the population of adults that require treatment would require more time and exposure. So I think we are just turning the corner here at 24 weeks after 40 years of bone disease.

And so our expectation is that over a year or two, you would have a better understanding of what the overall benefit in clinic would be. But we think this data is important enough to support an indication in adults. Now in terms of the forum, we haven't publicly announced what forum. So we are expecting to put this into a scientific forum.

There are several out there. I won't say what the plan specifically is. But many of our important data have come at the ASBMR meetings in the past. So that's a meeting where there has been a lot of bone data. But we haven't set at this point where exactly the data will come out..

Okay. That's really helpful. And I guess one unrelated question on Ace-ER. There was recently a publication that came out on a first-in-human Phase 1 study of ManNAc.

And just kind of curious how you are thinking about perhaps the competitive landscape in GNE Myopathy? If anything has changed at all? Or perhaps stayed the same? Or I guess high-level how are you thinking about the landscape here?.

Yes. There has been a program initiated in NIH for ManNAc and we have been talking about here and there in the past. It's gone very slowly. The data that look at ManNAc versus sialic acid suggest they both work including the most recent data from NIH in animals. Their hum program is very early stage. At this point, we haven't expressed much of a concern.

I think our future is determined by our own success in our own program and if our program is successful and we launch we will be the first substrate replacement therapy available for patients. At this point, I don't think there is any evidence to say ManNAc would be better than sialic acid, but it's out there. It's gone very slowly.

So we haven't at this point concerned..

Okay. Thank you very much..

Thank you. Our next question or comment comes from the line of Joseph Schwartz from Leerink Partners. Your line is open..

Thank you very much for taking the questions. This is Dae Gon, dialing in for Joe. So two quick ones for me.

With regards to the bone data that was disclosed today for burosumab, can you put that data into a little more commercial context? So how you envision this to have a material impact, if any, in terms of commercial uptake in adult population and how that compares to your thoughts on pediatric uptake? And then the next question is on the rhGUS, so can you remind us what kind of initiatives or executions you have been conducting since the Phase 3 data we had readout last year ahead of filing BLA and MAA mid this year? Thank you..

Okay. So on the bone data, I think what the bone data says that we are actually healing the underlying bone disease to some degree, which means and we expect that the osteomalacia is improving, which is the fundamental disease that exists in adults that leads to the fragility of the bone and reason they fracture in the first place.

So we think that treating that problem is changing how bone is healing and allowing bone to heal more completely. We think then it is evidenced that the bone disease of adults can be improved with burosumab and we expect to have more data on that later in the year when we have the Phase 3 biopsy or bone quality study readout information.

What we think when we talk to doctors is that treating the underlying osteomalacia is a reason to treat. Osteomalacia the known bad bone that doesn't function and it makes patients risk both for fracture and other deformities and problems as well as pain and symptoms. So I think it's very well recognized.

If you can osteomalacia which usually is improving bone quality that you might find the biopsy study, but also is improved healing of the fractures that are the consequence of osteomalacia we think that that is a basic reason why patient would get treated by their doctors.

We think with the symptom data we have just shows that that is translating the patients, at least it within the 24 week time frame, the patient start to feel the difference, particularly in stiffness, but we expect over time the other symptoms would improve based on what we have seen to-date and what was seen in the Phase 2 study previously.

So our view right now is that the data helps support the potential of treatment of adults with XLH and we think that the combination of that with other data will be supportive in the adoption of this as a new treatment for XLH adult. Now for rhGUS. From the time of the Phase 3, we have been collecting all of our data.

We have treated some patients in the under five program as well. We feel we haven't talked too much about while we accumulate some patients who are under five on treatment. We collected all that data, preparing the filings and we said we would file first half which we will announce once the filings are accepted.

So the process has mainly been focused on that. From a commercial standpoint, our focus is only on patient identification education. Like a traditional NPS program, really all of the work is all about patient identification.

There is really no other types of market development work you need to do other than to find patients and doctors that are treating them. So we continue to do that and are building our global team in Europe and starting our Latin American team and so them and contractors are working through the identification of patients with MPS 7 wherever they are.

And in a few cases, treating them early, if necessary, if there is younger year of age and are in second need treatment, we have been initiating some of those patients on drug..

Emil, are you able to comment on how many patients you have identified to-date on the MPS 7 side?.

We haven't put out the information yet. I think at some point when we are getting ready to launch we can talk about where we are at. But we haven't really put out the numbers yet. We have said in the past that we expect there to be, if we found every single person in the world diagnosed in the adult world, about 200..

I still think that's right and we are continuing to do the work to get there..

Great. Thanks very much..

Thank you. Our next question or comment comes from the line of Tazeen Ahmad from Bank of America. Your line is open..

Hi. Good afternoon. Thanks for taking my question. Emil, just wanted to get some color from you on whether or not there is some secondary endpoints that we should be looking for in Ace-ER study? And also would the upper extremity composite endpoint itself be sufficient for a U.S. approval, in particular? And then I have a follow up..

Yes. So in the secondary endpoints, there is going to be lower extremity composite, LEC and the knee extension which is another leg and then the mobility score FAS and then the other endpoints would be upper extremity FAS. So I would look at this is an upper extremity focus in the primary endpoint.

Secondary focus is in the lower extremity in the secondary endpoint. And in the U.S. and Europe, they accepted upper extremity strength primary endpoint as the prior data for execution.

The EMA and the FDA would certainly like to see if it works generally fast enough and that's why those date are in there and how we design, who is included in the study. It was not stated to be a requirement. But particularly EMA was interested in seeing some effect on lower extremity.

And there was acceptance that it could be in the lower extremity muscle strength composite rather than something like walking. In the U.S., they are comfortable with the upper extremity composite. Even without supportive data, it was sufficient to prove the benefit because it's how patients function.

So their mind of its strength is an obvious patient function endpoint, therefore clinical and intrinsically meaningful. So of course when you get data, you will always have to explain it.

And we think we have the types of endpoints built into this program that will help us provide clinical context, if necessary, as the first treatment ever for this disease.

So I would expect that, there is not a lot of standard for what you should be doing but these patients are losing the ability to walk over 10 to 20 years and their upper extremities are failing. They often end up quadriplegic. So it doesn't take too much imagination to see if you are stabilizing the strength and are not losing it.

So that's going to add up over time to be something clinically meaningful. Our long-term extension study where we had patient on drug for a long time where you project our natural history for our placebo control groups, you can see that a differential would grow over time, which we think is a very clinically meaningful thing for these patients.

And even if the study is only 48 weeks, it's not hard to imagine that that differential in strength change will add up to a lot when you talk about the years of lifetime exposure to this disease..

Okay. Thanks for that color. And then for KRN23, just if we could go back to you recent data for the secondary endpoints as you discussed them with FDA.

Did the agency indicate to you that anyone of those particular secondary endpoint might be more important than the other? In your view, is it problematic that the pain secondary endpoint was not that big?.

Well, the FDA received our modified plan and we had no indication that they would give us one or two, but our expectation is that we add a multiplicity adjusted analysis, which show there is a clinical meaningful effect on stiffness. They were aware of stiffness in the past. They referred to the clinical problems of pain and stiffness to us.

So I feel comfortable they are aware stiffness. I will tell though, on a lot of FDA meetings I have been, it is very hard to get them to say if this happens we are going to approve you. They just don't like that conversation.

I never ask that question because it puts them in a position of trying to make a decision of hypothetical and that's not fair to them. So our view is that we have shown clinical benefit with stiffness. We can demonstrate its meaningfulness. They were aware of the analysis method.

The multiplicity analysis says, look, we e have adjusted for the probability testing three times when that would alter your rigor and we have shown clinical meaningfulness in stiffness. In addition, nominally it was significant physical function and pain was a strong trend.

So it's one positive, too strong trends and now additional information on the 50% of patients that have fractures showing bone healing. We think that that's independently supportive data that demonstrates clinical benefit, we believe. Of course, for the agency, it's going to become a review issue, no doubt. But we will have a pre-BLA meeting.

We will have a first discussion about it and we will update you at that point..

Has that meeting been scheduled?.

Well, we don't talk about when they are scheduled or what day they are happening but we are obviously working through that process to get this done as promptly as possible. Because obviously, we feel filing this program is probably the most important activity the company would be doing..

Okay. Thanks..

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

Arlinda?.

Ms. Lee, you may need to unmute your phone..

I unmuted. Hi guys. Thanks for taking my questions. I have a few on KRN23, particularly on the pseudofractures and active fracture improvement.

My understanding is that on the pseudofractures side, that's a little bit more recalcitrant types of fractures? Do you have any further granularity on the breakdown?.

Well, we did note that it was having 12 set of fractures were just real recent straight fractures and the others were pseudofractures. But both are fractures. Both are having osteomalacia. Pseudofractures is just sort of incomplete healing in their defect in the bone than when it will actually heal.

I would say to you that these were mainly in the weight bearing parts of the patient. So they are clinically meaningful relating to the weight of pressure of walking and so forth.

What I would say to you, is I think that the fact that you are healing these types of fractures which are things that happen to people, for example people of osteoporosis drugs as an adverse events and all those don't heal very well.

So we feel pretty comfortable that the fact we are taking these fractures and healing them to a significant percentage within a 24 week period is a meaningful change in the bone health, which is allowing these fractures to heal. But most of the fractures or pseudofractures, as I said, both types of fractures were healed to a similar degree..

Okay. Great. And then I guess I had two other questions on KRN23.

One, can you maybe talk about what kind of powering assumptions you are assuming for the Phase 3 pediatric trial comparing versus active control? And then also maybe on the financial side, can you maybe walk us through what happens after the five-year profit share?.

Well, I will do the Phase 3 P and I will let Shalini handle the after the profit share. So the Phase 3 P study is a randomized controlled study that's been enrolling and it's not blinded. It's not a blinded study. So you just can't really blind treatment.

So it's a randomized controlled open label study and it will look at rickets scoring as we have done before comparing the two treatments to each other. It's superiority design. We are looking for superiority of KRN23. At the last line, we will do noninferiority, if you will.

If you really are going to go out with a new drugs that's meant to improve the health of these patients, I think you need to demonstrate superiority. There is not much benefit in coming out with a new drug that's no better than historical data.

We think from the data we have seen and based on our review of data from other patients treated on current care, that the treatment effect size that we are seeing, KRN23 will be larger and we think that's because we are improving phosphate to the normal range whereas oral phosphate therapy barely moves phosphate at all.

I will let Shalini answer the question on the five-year profit share..

Sure. So just to backup a little bit, during the first five year period, post launch of the product in North America, it's thus called a profit share period, under the collaboration agreement with KHK.

And during that time, what happens is, Ultragenyx pays KHK for supply of the product and then the remainder of the cost are split 50-50 between the two companies.

Now five years post launch, KHK wanted to take over the majority of commercial activity for the product, but Ultragenyx did not want to pay 50-50 for a large company as commercialization cost, just because the cost structures are very different between large and small companies.

And so the structure changes at that point into a royalty which is a royalty to Ultragenyx in the mid to high 20% range on net sales.

Does that help?.

Do you have to pay KHK for product afterwards?.

No. We do not. We only receive the royalty and that royalty is intended to mimic the economics of the profit share period..

Okay. Thank you. And then maybe just one more follow-up on the Huntington's Disease trihep. I know somebody asked a bit earlier, clinicaltrials.gov lists this as a primary completion date of June.

If it's going to be presented at a medical conference or if there is any top line data to be had, would you press release that or what kind of data information are we going to get in that?.

Yes. Well, we obviously don't control release of that data exactly because it's hers, but if it was being presented at a scientific meeting, obviously since we are supporting as material then we would coordinate with her on what we would do before a release at a meeting..

Okay. Thank you..

Thank you. Our next question or comment comes from the line of Liisa Bayko from JMP. Your line is open..

Hi.

How are you?.

Hi..

I just wanted to ask some question on the FAOD study.

Where are you in terms of your discussions with FDA? When we would expect more details on what you are thinking for Phase 3?.

Right now, so we are still working on the FAOD design. We have said that we are moving toward in the direction of doing event-based study because we think it would show more substantial value of the product. And in the current scheme, I am concerned about prices and value.

We think something that reduces hospitalization, days in a hospital will just be a more compelling story than exercise tolerance. So we are looking at that. We need to do the feasibility, understand how to construct before we present that to FDA. So we are doing that design work right now.

We would expect to talk with the FDA soon and we haven't really set a timeline for getting that study going. But we are excited about that data. And I think investigators in the field are actually pretty excited too about the effect that we are seeing.

So we just want to make sure when we pull the trigger on a study of that type, that you set it up right and that you power it and you design the number of sites and so to end up with a study that executes as promptly as possible and generate the results you are expecting..

And in terms of any formulation changes that you are planning, where are you with that, if you could give us an update, that would be a great? That's my last question. Thank you..

Sure. Our we are sticking currently with the oil formulation. We had done some work in a powder which had some issues and we haven't gone back and restarted a powder. But there is certainly possible ways to generate a powder and we have just focused in on using the oil. We have got better understanding how to manage the oil and tolerability.

And there have been patients on drug now 15 years or so. So it can be tolerated in long-term. The techniques involve mixing it with food and other things that help emulsify it. And the people have gotten into the habit of doing it and tolerated long-term.

But we will still look at the possibility of a powder at some point, but we were not doing that right now. The first powder we made did not meet our specifications for moving forward..

Thank you..

Thank you. Our next question or comment comes from the line of Matthew Harrison from Morgan Stanley. Your line is open..

Hi. This is Cyrus, on for Matt. So there has been some debate with investors around the clinical meaningfulness of the adult XLH data that recently came out. Since you guys had that data in-house, I am sure you have shared it with your key XLH KOLs.

Can you comment on their views on the data? And then how this could impact their adult patients?.

Well, we normally don't discuss what the doctors tell us in our story. We are comfortable that if we are treating the osteomalacia and we are healing fractures and people patient feeling that is a potential reason to treat patient. I think there was a good call that was done with Dr.

Carpenter that's probably available to people to look at and I think Dr. Carpenter's view is that this was good data and that it showed the patients are changing from 40 years of a bone disease, starting to improve and he felt comfortable as that was important.

He, like many doctors, are comfortable that changing the phosphate normal range is treatment of the disease. If you fix the phosphate, you fix the disease. We are issuing more about demonstrating that effect for FDA.

While the focus of Phase 3 was about symptoms, we think the fracture data provides the kind of hard data, so to speak, of that will support that what you are seeing with symptoms is based on a change in the bone, at least to some degree and we think that just support for a regulatory pathway. From a doctor's standpoint, I think Dr.

Carpenter's view is pretty common that change the phosphate, you change the disease and that 40 years of bone disease will take time to fully reverse in some part of the disease, like osteoarthritis which has progressed, it will probably not be reversible. So we think there is a number of symptoms that we might benefit even in adult patients..

Got it. Thank you..

Thank you. Our next question or comment comes from the line of Yigal Nochomovitz from Citigroup. Your line is open..

Yes. Hi Emil. Thanks for taking the question. Just going back to the burosumab Phase 3, obviously there is a lot of secondary outcome measures, the 12 I believe and then the five of the other outcome measures. You have reported on the three key ones for the clinical outcomes and then you just reported on the radiographic data today.

What does that mean in terms of the other secondary and other outcomes that you haven't discussed? Are we going to be seeing those? Or is the assumption that you didn't see effects there that were satisfactory.

So for example, taking a walk is another outcome, patient global impression and then there is whole long list of biomarkers among the secondary outcome measures. Thanks..

Thanks Yigal. So on the biomarkers, we did mention those, I thought on the Phase 3 call that the bone biomarkers actually increased a lot to turnover a bone. So the P1P and the CTx and the bone-specific alkaline phosphatase, all increased substantially by 12 weeks and still up at 24 weeks. That's not surprising and we are seeing some bone healing.

Those markers would suggest that it's a bone synthesis and bone turnover occurring. We haven't, but we normally don't put out every endpoint. We would expect to do that at a scientific meeting.

We put the fracture data out, because it was distinctly unique and relevant to the healing that's going on in these patients and we thought it was complementary to patient data. But we will put out the data at a major meeting in the future..

So there is still the potential to see something on, for example the six minute walk, potentially?.

Yes. There is all the data in there to be shown. But it will come out, we would expect later at a major meeting..

Okay.

And then in the pre-BLA meeting, I mean you didn't hit on the pain endpoints based on the [indiscernible], but are you still going to make an argument to the FDA that that pain claim should be in the label or considered in the label?.

Well, I don't know that knowing historically with FDA that they are pretty, I think they are fairly strong on statistical significance by predefined statistical criteria for a labeling of endpoints.

But I think that the pain data are simply, even though they are strong trends, are supported across-the-board what you are measuring in patients there is something happening for them. I think it's pretty clear that pain is complex in these patients. I don't think not having pain on the label, I don't think it really matters.

The pain is secondary to a disease process. We are treating the disease and the pain should get better. So the fact is, this is not an analgesics. You can't compare to BPI Question 3 giving another oral opioid or something where you are directly effecting pain. We are affecting underlying disease which is changing the pain outcome. So it's very indirect.

I think the stiffness is probably a direct effect of phosphate partly on muscle, maybe on bone and the physical function is kind of a synthesis of a number of clinical features. Both of those were nominally positive, right. So without multiplicity, those two are positive. The other one is strong trends.

The multiplicity just gives you, it's a second way of looking at the data to say, all right, there more than one secondary and this just a more regulatory way of saying, despite we get three, the results don't claim it meaningful, why I am still surviving the analysis.

I think the data on bone healing adds another dimension, the bone dimension to that study, which I think helps support that what we are seeing here is the fundamental change in biology where normalizing phosphate, it is training on bone, remodeling the bone, synthesis to heal the bone, the bone is healing as we can see and patients are showing effects of this normalization of phosphate on their bones and I think it ties now straight through from the mechanism of action all the ay through clinical outcome.

I think that's a strong story you can tell. Our view on treating XLH is, I would prefer myself in cases for the treatment of XLH, I rather not have a treatment just of one symptom because that's a narrowing view. I would rather have an indication to treat the disease and that disease manifests itself differently in different people.

So someone who doesn't have pain, I wouldn't really, they would be treated for some other symptom they have. The question is, are you treating the underlying disease and is that disease clinically meaningful across the whole series of different endpoints and approaches and I think it is and I think that's how the story will move forward..

Okay. Thanks. And just one more. What additional work are you doing on the commercial side to understanding of the XLH market in terms of patient identification, if you could comment on the status of some of the XLH registries out there in the states or in other territories? Thanks..

Well, I think obviously connecting both patients and not just key opinion leaders physician, but the secondary physicians out in the clinical practice treating patients is quite important. And the whole team has been working on identifying who are the doctors that treat XLH patients suing a number of data tools. They are buying and tracking.

And our team of MSLs and PDLs have been out there tracking and validating doctors and patients and developing essentially a map of the United States and where everyone is.

That work has been progressing and we are probably going to increase the patient diagnosis work substantially later this year to try to discover where are all the patients of XLH that we can find and to set ourselves up for the next step of commercialization, assuming that process gets approved.

That's the biggest effort that's going on is patient diagnosis and out there. And the XLH network is the main U.S. patient group. They are relatively young group. We provide them support and they are doing more outreach and have been active now in organizing patients.

But as you think that for a disease like this, without really any specific treatment, except for oral phosphate, that there is this opportunity to reach out to people who may have not part of the system, that are out loss with secondary doctors, to capture those people earlier on the process in the launch and pull them in to the opportunity for a new approach to treating XLH that they probably thought would never happen.

And so that's where our focus has been, finding doctors and patients..

Great. Thank you..

Thank you. [Operator Instructions]. I am showing no additional audio questions at this time. I would like to turn the conference back over to management for any closing remarks..

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

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