Ultragenyx Pharmaceutical Inc (RARE) 2015 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Ultragenyx Pharmaceutical's second quarter 2015 financial results.

(Operator Instructions)

As a reminder, this conference is being recorded. And now I'll turn the conference over to your host, Rob Anstey. Please begin.

Great, thank you. Good afternoon, everyone, and welcome to the Ultragenyx Pharmaceutical financial results and corporate update conference call for the second quarter of 2015. We've issued a press release detailing our financial results which you can find on our website at www.ultragenyx.com.

With me today are the following members of the Ultragenyx management team. Emil Kakkis, CEO and President; Shalini Sharp, CFO; and Sunil Agarwal, CMO. We'll keep our prepared remarks brief in order to allow time for the question-and-answer portion of the call.

But first, I would like to remind investors that this presentation contains forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Including but not limited to statements regarding the expected release of data from clinical studies, the initiation of additional clinical studies and the designs of same. Plans regarding ongoing studies for existing programs, and the possibility of being able to file for an approval and our intent to do so where permitted.

These forward-looking statements represent our views only as of the date of this call. And involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements.

Such risks and uncertainties include, among others, the uncertainties inherent in the critical drug development process, actions of regulatory authorities, the timing of our regulatory filings. And other matters that could affect the availability or commercial potential of our drug candidates.

For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in the forward-looking statements, as well as risks relating to our business see our quarterly report on Form 10-Q for the quarter ended March 31, 2015, filed with the Security and Exchange Commission on May 12, 2015. Our quarterly report on Form 10-Q for the quarter ended June 30, 2015 that will be filed today, and our subsequent periodic reports filed with the Securities and Exchange Commission.

I'm now turn it over to Emil.

Thanks, Rob, and good afternoon, everyone. Thank you for joining us on the call today. I will start things off with a quick update since the last call, Shalini will then provide the financial update and Sunil will provide an overview of our progress on our clinical pipeline.

It's been an exciting few months at Ultragenyx since the last call. And we're reported data from our KRN23 program, raised substantial funding, expanded our senior manager team, and pushed forward our late-stage programs. Regarding KRN23, it reached number of significant milestones since our last earnings call. First, we reported the first set of data on clinical study for KRN23 in pediatric patients with XLH. We released 16-week data for 36 patients, which showed an increase in serum phosphorus in all patients, consistent with the data previously generated in adult XLH patients.

Following that, in early July, we released interim 4-week 40 week data for the first 12 patients showing an improvement in rickets bone disease scores, beyond what was achieved with standard of care at baseline. We're encouraged by these results, and we look forward to releasing additional 40-week data in 36 patients in Q4 of this year. Sunil will provide more detail on these clinical results later in the call.

We also recently announced the details of our Phase 3 program KRN23 in adult XLH patients. That two-study program, including a randomized control study and the small bone biopsy study will kick off later this year.

Additionally, we held discussions with the European Medicines Agency, or EMA, about the KRN23 program. In those discussions, the EMA indicated that we may be able to file for conditional approval for KRN23 based on the 40-week data on 36 patients if a positive benefit risk is obtained in the treating of bone disease, combined with the existing adult data generated to date. We now look forward to following up later this year with both EMA and FDA to discuss the recent rickets data, and determine appropriate next steps in our development program.

KRN23 was the highlight of the last quarter, but we're on track for a number of key milestones in other programs over the next six months. So for the remainder of 2015, these milestones include Triheptanoin compassionate use data in infants with FAOD and life-threatening cardiomyopathy that will be presented at the SSIEM, the Society for Inborn Errors of Metabolism in Europe.

We'll have Triheptanoin data from our ongoing Phase 2 study in FAOD patients in Q4. We'll have Triheptanoin interim analysis from our ongoing Phase 2 study in Glut1 deficiency patients, with a focus on the seizure aspect of the disease. These data will unveil either late this year or early next year.

We be filing an MAA for ACR for conditional approval in Europe for GNE myopathy. In addition, KRN23 initial data from the Phase 2 study of tumor induced osteomalacia will be released. Either late in 2015 or early 2016.

The KRN23 40-week data including more rickets data on the 36 patients from Phase 2 study in pediatric XLH will get released. And initiation of a KRN23 Phase 3 randomized double-blind placebo-controlled study in adults with XLH will get announced.

To support these and other efforts, including the three Phase 3 studies that we'll be running by the end of 2015, we recently raised additional capital. We brought in $287 million in net proceeds to accelerate commercial launch preparation for Ace-ER, rhGUS and KRN23 to invest in early-stage research and potential new programs. And to support the continued late stage advances of our programs.

To drive our development and commercialization efforts, we recently announced two new members of the executive leadership group. Jayson Dallas joined us as Chief Commercial Officer, leading our global commercial efforts. And will first focus on developing our global commercial team and our European, US and Latin America operations.

John Pinion has joined us as Chief Quality Operations Officer. In this new role, John will lead our global of QAQC functions that manufacturing and clinical development. As well as support translational research efforts to develop early pipeline projects from his analytical science and research role.

Both of these positions are critical as we move forward toward the commercial stage. Jayson and John have a deep background in building and leading successful organizations, including both most recently managing significant operations at Roche Genentech. We welcome them both to Ultragenyx.

We also recently announced that Dan Welch has been elected Chairman of the Board. Dan's extensive experience including his role as Chairman and CEO at InterMune, and most recently his role as an Executive Partner at Sofinnova will be a valuable asset going forward.

It's been a busy 2015 for Ultragenyx so far. And the rate of pipeline advancements and [inflows] is expected to continue to increase. In the next 12 to 18 months, we'll have approved concept Phase 2 data or pivotal Phase 3 data from all six of our clinical programs. And even more significantly, may be on track for US or EU filings for as many as three of those programs in the next 18 months.

I'll now turn the call over to Shalini to walk through the latest financials.

Thanks, Emil, and good afternoon, everyone. We issued a press release earlier that included a financial update, which I will briefly summarize.

Our second-quarter 2015 results included total operating expenses of $30.1 million. Research and development costs accounted for $23.1 million or 77% of our operating expenses. Our Phase 3 programs, Ace-ER and rhGUS, accounted for the greatest proportion of R&D costs in the first half of 2015, as well as the largest increases in expenditure relative to the first half of 2014.

Expenses also increased for both Triheptanoin programs and both KRN23 programs, as compared with the first half of 2014. As a reminder, we share KRN23 development costs 50-50 with our collaborative partner Kyowa Hakko Kirin. Costs for our preclinical translation research programs also increased over the prior-year periods.

OpEx increased significantly from the second quarter in 2014, due to the conduct of multiple late-stage clinical studies. Manufacturing costs related to clinical supply of multiple programs. Investments in our commercial infrastructure and patient identification efforts, and general and administrative expenses to support these activities.

Total net loss for the second quarter of 2015 was $29.8 million or $0.83 per share. Compared $13.6 million or $0.45 per share for the second quarter of 2014.

Net loss for the quarter ended June 30, 2015 included approximately $6.6 million or $0.18 per share in non-cash charges, such as stock-based compensation, amortization of premiums on investment securities and depreciation and amortization. As we continue to build out global commercial capabilities and advance our clinical stage and preclinical pipeline programs, we anticipate that our expenditures will continue to increase in future quarters.

We ended the second quarter with $326 million in cash, cash equivalents and short-term investments on the balance sheet. That does not include the $287 million in net proceeds raised from an underwritten public offering of common stock in July of 2015. We do not have any debt outstanding.

I will now hand it over to Sunil to provide the development update.

Great, thank you, Shalini. I'll now provide an update on our clinical progress over the last several months.

As Emil mentioned, we recently released data from two separate analysis from our Phase 2 study of KRN23 in pediatric patients with XLH. The first of these was the 16-week analysis in 36 patients that showed that all patients had increases in serum phosphorus from baseline after treatment with KRN23.

At the end of the 16 weeks, the majority of patients in both the monthly and biweekly dosing groups reached the normal range of serum phosphorus. Additionally, the number of patients achieving the normal range continued to increase after week 16, as patients continued to have their doses titrated as needed.

Increases in TmP/GFR and vitamin D were both also observed in the 16-week analysis. Overall, these results met our expectations and are consistent with the data generated to date in adult XLH patients. From a safety perspective, no serious adverse events have been reported and no patients have discontinued. The most common adverse events have been injection site related, and all of them were deemed mild in severity. No significant changes in serum calcium, urinary calcium, or parathyroid hormone were observed. And no patients had serum phosphorus levels above the upper limit of normal.

The second set of data included the first interim look of KRN23's impact on the underlying bone disease in these patients. The analysis included x-ray data from the first 12 patients, evaluating their degree of rickets via the Thacher Rickets Severity Score. The mean rickets score decreased by 58%, going from 1.4 at baseline to 0.6 at week 40. 8 out of 11 patients with rickets at baseline demonstrated an improvement. Of which, three patients no longer exhibited radiographic evidence of rickets at week 40.

Of the 12 patients, six received biweekly dosing, and six received monthly dosing. One patient in the biweekly dosing group did not present with the radiographic evidence of rickets at baseline, and was excluded from the analysis. All five out of five patients in the biweekly dosing group demonstrated improvement in rickets. The mean baseline rickets score was 1.5, and changed to 0.3 at week 40, representing an 80% reduction in the biweekly dosing group.

Of the six patients in the monthly dosing group, three out of six demonstrated improvement in rickets. Two patients did not show a change, and one patient worsened by 0.5 points. The mean baseline score was 1.3, and changed to 0.8 at week 40, representing a 38% reduction in rickets score in the monthly dosing group. Overall, these interim data are encouraging. As they are the first indication that KRN23 may improve rickets, beyond what can be achieved with standard of care. No serious adverse events were reported, and no patients have discontinued. Mild injection site reaction were the most common adverse events.

Pediatric Phase 2 data in 36 patients at 40 weeks are expected in Q4 this year. We're also expanding the pediatric trial to a total of approximately 50 patients, and expect 40-week data on all 50 patients by mid 2016. The additional 40-week data will include rickets, as well as safety and pharmacodynamic results.

Prior to having the 12 patient 40-week analysis, in a meeting with the EMA, the European agency indicated that a conditional approval filing may be possible based on positive 36 patient 40-week pediatric data, and data from the completed Phase 1.2 and ongoing Phase 2 extension studies in adult XLH patients. Confirmatory studies would be required to maintain and convert any such conditional approval to full approval.

Based on FDA and EMA feedback, we plan to initiate a Phase 3 program in adult XLH patients by end of year which will include two studies. The first is a pivotal Phase 3 randomized double-blind placebo-controlled study of KRN23 versus placebo with approximately 120 patients. Serum phosphorus is the primary endpoint at week 24, and the brief pain inventory will be a key secondary endpoint, also at week 24.

The second study will be a smaller open label study in 10 patients, evaluating osteomalacia pre-and post treatment with KRN23 via bone biopsy. We're encouraged about the recent progress with the KRN23 program. We plan to follow up with both EMA and FDA to gain more clarity on the next steps in the development program.

Moving on to Triheptanoin. Several data points are expected to be released by the end of 2015. First will be compassionate use data in infant FAOD patients with severe cardiomyopathy. At the SSIEM conference in September, five case reports will be presented. Many with life-threatening disease, despite treatment with a standard of care, medium chain triglyceride oil. Data from our 29 patient Phase 2 study of Triheptanoin in a broader and older FAOD population will be released later this year. The study is a learning study and is measuring a wide range of musculoskeletal, liver, and cardiac endpoints with the goal of determining the best signals of activity to further evaluate in a potential pivotal trial.

An interim analysis from our ongoing Phase 2 study of Triheptanoin in Glut1 deficiency syndrome is also planned around year end 2015 or early 2016. The primary focus of the study is the seizure manifestations of the disease.

Based on the positive investigator sponsor trial results in the movement disorder manifestations of the disease presented at AAN earlier this year, we're in the planning stages of a second Company-sponsored study in Glut1. The planned study design is a randomized double-blind placebo-controlled crossover study. We plan to discuss this study design with the FDA by year end.

The final two brief updates are for our most two advanced programs. First, for rhGUS, our pivotal Phase 3 study is fully enrolled with 12 patients as of June 2015. The top line data are expected in mid 2016.

In addition to this Phase 3 study, a few weeks ago, we initiated a Phase 2 study in patients under five years old with MPS7. The study will include patients with a severe infantile presentation called non- immune hydrops fetalis. Interim data from this study are expected in late 2016.

We're also now treating two infant MPS patients under named patient programs. One in France and one in Turkey. We'll continue to evaluate named patient treatment requests as they come in.

The next and final program is aceneuramic acid extended release, or Ace-ER. We're currently enrolling GNE myopathy patients in the pivotal Phase 3 study. That trial kicked off in May of this year, and is expected to report data in late 2016 or early 2017. The primary endpoint is a composite of upper extremity muscle strength at week 48. This is the same endpoint used in Phase 2, which showed a preservation of upper extremity muscle strength over 48 weeks. Based on the Phase 2 data, we intend to file for conditional approval in Europe this year.

I am pleased with the milestones our team has reached thus far in 2015. I look forward to updating our investors, the physicians we work with, and the patients we serve as we generate more data and advance our pipeline.

I'll now hand it back to Emil.

Thank you, Sunil. We made substantial progress of our pipeline in 2015 so far, and there's more to come in the second half of the year. Our significant cash balance will support these aggressive development efforts as we continue our ability to attract top-notch talent as we expand in all clinical critical functions.

Before closing out my comments, I'd like to remind listeners that we will be holding the first Ultragenyx Research and Development day. We will be in New York on December 3. More details will be provided later, but we hope to see many of our shareholders there.

Thank you, everyone, for listening. We can now move on to the Q&A session, and can the operator please provide the instructions.

(Operator Instructions)

Eric Schmidt, Cowen and Company.

Good afternoon, congratulations on all the process and thanks for taking my questions. First for Emil or Sunil, on the Triheptanoin study in FAOD, the Company-sponsored study.

I guess that's the next major Company-sponsored event. And I know you're calling this a learning study, it has multiple readouts and endpoints. But what ideally would you like to see from the trial in order to be convinced that you have differentiation versus MCT oils?

I'll start with that, and maybe Sunil can provide additional comments. The types of patients that are enrolled in the study are patients who are on standard of care, which usually included MCT oil, who were failing standard of care and were having significant clinical problems. The largest group of those patients have problems with rhabdomyolysis or muscle disease, excess intolerance, essentially skeletal muscle problems.

And many of the patients have impaired ability to walk around or play or go to work, and often are very sedentary to avoid worsening their problems. So in those type of patients we were hoping to look at some impact on their skeletal muscle disease, which might translate into either improvements in their walk distance or their excise output on the cyclecyclogometer, or in perhaps their energy efficiency index, how well their heart essentially is being able to pump out and function during exercise tolerance events.

We will look at rhabdomyolysis and creatine kinase endpoints as well, but the size of the study will probably not be large enough to be able look at, let's say, how many events of rhabdomyolysis they have. So we're going to focus more on the physiological measures in skeletal disease.

In the hypoglycemic patients, they're a smaller group that qualified they were having ongoing and recurring hypoglycemic problems. Many of them are constantly treated with food or maintain to avoid hypoglycemic. So we're primarily looking at how well they do when they take a fasted blood glucose or when they are in fact how many events per day are they having of needing supplementation or symptoms suggestive of hypoglycemia.

We'll look at their livers too. Because usually in these patients, the livers can be enlarged or have elevated transaminase and other things related to break down of fatty acids and the inability to produce energy. So that is the kind of thing we look in those.

The cardiomyopathy group in the study, and relative -- I think there was just one who qualified based on cardiomyopathy issues. And so we won't really learn very much about cardiomyopathy in the study.

What was happening is that the patients who might have qualified with cardiomyopathy were actually landing in the emergency room or in the ICU. And we were getting urgent emergent calls for help, and we decided not to risk the patients lives, and would go ahead and let them get treated in the invasive compassionate use program. There's five of those patients that are in the SSIEM release that's coming up.

So I would look to more of that release to tell you what you see in patients who are on standard of care, and are having cardiomyopathy problems. And they're being treated with Triheptanoin.

So if you have to summarize it, Eric, the skeletal muscle part of the phenotype is the most common phenotype that is in the study. And so our goal would be to show that their muscles are functioning better in some physiologic measure. Either the ability to how much energy they use and they can create in a cyclogometer at a particular heart rate, or how far they walk, or how much their energy efficiency looks like.

And those are things that are good measures of whether their muscles are not functioning optimally, not using energy optimally. Which are, we think, part of the problem you see in FAOD patients and why they have so much excise intolerance.

It's kind of a long answer I know, Sunil, if I left off something.

No, actually I think you covered it well, Emil. Just to remind people as well, this is the 24-week 6-month analysis, but the study doesn't end there. We do want to continue to follow for long-term potential benefit or signal generation, so the study continues on for another 54 weeks. So again, 24 weeks by end of this year, but we will continue to follow these patients longer-term.

And then Emil you mentioned the five compassionate use cardiomyopathy patients. What would be the normal prognosis for such patients not treated with trihep?

Many of the patients end up with cardiomyopathy; basically they die from their cardiomyopathy. And there are patients treated with standard care that will bounce back some, but many of the patients who start having that problem are of severe FAOD type and the mortality rate is quite high. And in this case, these are patients who are in the ICU, many of them are on pressers, on vascular support or cardiac support function devices and things.

So they were in pretty sick condition. So the data will review what their hearts look like in terms of echocardiographic function, and how did they do when put on Triheptanoin.

Thanks for that. Maybe one quick one for ShaIini just on the expenses. It looks like there was a pretty decent sized bump up in Q2, and you alluded to continued growth. Are we going to grow at a similar pace, or just grow more gradually off of the Q2 base?

I think we will continue to grow at a fairly significant pace, Eric. So we do have multiple programs heading into phase 3, and we're trying to now build out the commercial infrastructure in a really rapid and efficient way.

So we do expect that to continue to increase. And then as I noted in my comments, there's a significant non-cash component in there as well. So I would pay attention to that too.

Great, thank you.

Cory Kasimov, JPMorgan.

This is Britney in for Cory. Thanks for taking the questions. So with the majority of your products in mid to late stage development, can you comment on how you're thinking about feeding your pipeline?

Are you actively looking to add any additional products, and if so, what type of products would you be looking for? And then just quickly on KRN23, is there a potential for accelerated approval in the US as well? Thank you.

So I'll start with the pipeline, and then Sunil can talk about the regulatory pathway for KRN23 in the US. So we're actively -- obviously, when we have five or six [prog] in the clinic, we were in the last couple of years working on driving that portfolio forward. And that was our job one with the Company.

Over the last year and a half though, we have started and have done quite a bit of work on a number of business development opportunities. And we are actively building out the pipeline in the translational research group. We currently have two programs that are in preclinical.

Now we've disclosed galactosialidosis, or UXO 4 before. We haven't disclosed the other one. And in general, what I will tell you is, we're not going to normally disclose our stuff that is pre-clinical. We'll disclose things in general when we're headed to an IND where we know we've got something in hand and we're ready to proceed.

Our plan now with the two is to expand the five or six programs. There are several things we're looking at right now and working on. And we would expect to be doing that in the coming 12-month period.

Some of those may get disclosed. Some may be disclosed based on the deal that they are. And what our goal would be is to have five or six early stage programs to drive ahead, and with the goal of trying to get to about an IND every year or every of the year to keep refilling the pipeline and keep that pace up.

We definitely don't want to have a gap where everything moves to phase 3, and suddenly there's nothing behind it. So we are aware of wanting to keep that flow going. And I think we're seeing a lot of great opportunities.

To answer another question no one has asked yet. But people always ask, well how are you competing for these assets? There's so many people out there.

The truth is, a lot of diseases that people haven't heard of, you haven't heard of, that have great strategies for treatment. And we are focusing on those things where people are not paying attention to that we think are really important opportunities. And we're willing to look at science that needs slightly more work, and maybe do that one -- answer that one critical question in our own laboratories if necessary to get us to a product that we can develop.

So I think there's quite a bit out there. I actually have not run into the problem. I think if you talk about the late stage or commercial assets, it's a lot of competition.

And while we look at them, I think it's less likely to be an effective way to go forward. In terms of what we're choosing, we look at ultra rare things, but we can't build a whole company on things as small as MPS7. We'll do one of those here and there, or we'll have at least a slot in our pipeline for that.

But we are looking at things that are orphaned that have clear metabolic basis that we understand the biology, both of the disease and the treatment. And we try to focus on really simple stories, and simple mechanisms where possible. Something is low or something is high, and we're trying to reverse that.

So we're finding a lot that I think there will be things added to the pipeline over the coming year. So I will let Sunil talk about the reg cap for KRN23 in the US.

Thanks for the question. I think one general comment is, we stay very close to FDA and EMA throughout all of our programs, and of course KRN23, so it isn't we talk to them on an infrequent basis, we talk to them regularly. So we've had the recent data set now, and we do plan to follow up with both agencies.

We've mentioned the EMA discussions. And with the FDA, our goal is to understand the next steps, specifically around the pediatric development program. Could there be a potential for something like that, yes, but I don't want to speculate on the chances of that because we just haven't had those discussions with the agency yet.

I would reiterate one thing. Is that the FDA previously had said that they wanted standard of care controlled study data for the product. That is a request they made of us before.

If we think that the data are compelling, then we can try to work forward on accelerated approval pathway. But I would point out that they reiterated the need for controlled data. And so it will require a significant amount of effort on our part and to look at the body of the data to make headway with them on a more rapid pathway.

That's right.

Great, thanks so much.

Heather Behanna, Wedbush Securities.

Hello. Thanks, and I apologize in advance for the background noise. Just a quick question on KRN23.

If you could talk about, are you rolling people over into an open label extension after 40 weeks? Can the dosing be adjusted? And if so, what kind of things would you be monitoring for durability moving forward?

I will let Sunil answer that question.

Yes, on the pediatric program, as you know, it's a phase 2 program currently, in the answer is yes, we will be rolling people over into an open label extension. But just to remind you, the primary study is up to 64 weeks.

And one of the other endpoints at 64 weeks is looking at growth velocity. So we look forward eventually to having that data as well and seeing what that data looks like.

But after 64 weeks, we think it's critically important to understand to your point, the long-term safety and efficacy of this agent. So, yes, we enrolling over those patients.

In addition to that, on the adult side, the phase 1.2 was completed. But those patients were not rolled over to extension originally, we have reopened an extension program and are recapturing those patients. So we believe in capturing that long-term extension data, to your point, across both adult and pediatrics.

Great, thank you.

Chris Hargleton, Jefferies.

Thanks for taking the questions. I just had a couple on KRN23. First of all, for the EMA, the potential for the conditional approval which you're going to apply for, what is that label going to look like?

Is that going to include both pediatric and adult patients? Or what is your view on what that might look like if you were to get the conditional approval?

Thanks for your question. This is Emil. We generally wouldn't predict what is on the label. But I will let Sunil talk about what we think we have data to support.

I think there's maybe one general comment about on pediatrics and adults. And maybe more so on adults. As we continue to do drug development, we also continue to work on understanding the disease burden.

Because I think that is critically important in rare diseases, especially also in XLH. We've done a lot of work in adults and the burden of illness, and what we're finding is that the adult disease, it can be pretty severe with respect to the symptoms they have.

So when we do go back to the EMA, our plan is to talk to them about adult and pediatrics, not just pediatrics. We have adult phase 1.2 data. We have now pediatric phase 2 data. So our plan is to have a discussion of the totality of the disease, and then determine with them what makes sense.

I think that they said that we do have data on adults. And they did the existing data would be fileable. But the question is, this is phosphate data primarily. But we do show bullmarker data, and I think you could look at the drug -- if you look at the -- holistically at a program, if raising phosphate improves bone disease in rickets, it means the osteocytes are seeing enough phosphate to make bone. Which to me is just a signal that essentially the phosphate levels we're achieving are clinically meaningful. And they are changing the bone in peds patients.

And we think that would be true for adults too. It's just harder to measure in adults, because their bone turnover is just slower and the timeframe is maybe longer. But so we think we would certainly want to seek both, but our best data certainly is in the peds area.

Right, okay. And then just touching on that same point, what kind of things can or what kind of data will get off bone biopsy study that you're talking about? Will it be bone turnover?

Will it be things like bone density? Just give us a sense maybe of what that might like.

That's a good question. Really, as you know, in adults, the osteomalacia is the issue. It's just the histology, the lack of architecture of the bone. So the way we simply describe it is bone quality. You'll be looking at really the cellular architecture of the bone, and the osteomalacia, by the histology, is very easy to recognize. And it can be very severe in these adult patients. So it's one of those things, when you see it, you see it. And by the end the study, after approximately a year of treatment, we will look again. So it's all about bone quality.

Okay. And then just one last question if that's okay. For the rickets score, obviously this was designed for nutritional rickets. And so the scale is pretty big in terms of what you might expect for XLH patients. Is there any concerns about what the sensitivity could be in that big of a scale in relation to XLH phenotypes? And response to treatment?

I'll let Sunil answer the question of the scale.

So it's a great question, and the score is 0-10. And I think without understanding or for someone who may not understand the disease or how the scoring system really works, one could maybe make the misunderstanding that if you are 5, that means you are in the middle of a bad disease. And that's absolutely not the case on how this scoring system works.

For example, when I've seen x-rays myself of a score of 3 or even 2, that's extremely noticeable and looks very problematic for the risks and needs for these patients. So when we look at how the scoring system is operating, scores of 2, 3, or even 1 are very noticeable by our expert independent reader, and when you talk to the specialist, they consider that a very meaningful disease.

In addition to that, to your point about sensitivity. It does appear very sensitive to have step changes. Based on the data we've seen, based on talking to the experts, and also the person who invented the scoring system, Dr. Thacher.

Great, thanks for taking my questions.

Arlinda Lee, MLV.

Thanks for taking my questions. Can you maybe provide an update on the named patients sales progress for Ace-ER? And then maybe you talked about how you think about the pipeline going forward. Could you maybe comment on the kind of pipeline that we might be seeing from the existing drugs that are in the clinic already, and your appetite for maybe adding additional indications? And what the timing of that might be? Thanks.

All right. We'll start with the named patients sales in the UX001. We are planning to pursue named patient's treatment for 001 patients. RMA filing is happening in this half of the year. We are working on the names of patients sales process for UX001. We think there's substantial interest on it. Our expectation would be to be working with investigators who want to treat their patients.

Because of the various rules of it, we will be focusing on people that don't qualify for the phase 3 study. Because if they qualify for phase 3, they should be in a phase III program, not in the named patients sales. And so generally in these type programs, we'll start looking in the key countries in Europe, where it's possible with investigators who have severe patients that don't qualify for our study. So that process is ongoing, we haven't initiated patients in named patient treatment yet in the UX001, but it's proceeding. It takes some time to work through.

The second question is, are we pursuing other indications for our current pipeline? I think right now, the pipeline opportunities for the current targets are set. But there are some things we're doing in investigator studies that could become part of the story. So we are adding the movement disorder to the Triheptanoin program, as you know, and I think we already discussed that. It's part of the Glut1 indication.

We are supporting an investigator study on Huntington disease as well, which is a 100-patient randomized control study. So not an insignificant IST that is up and running. So that is another potential indication that could come in if the study shows efficacy and safety in that indication. So that would be a potential another -- a way for trying to move forward.

There are actually a number of ISTs ongoing for Triheptanoin, and some of them can be discovered by going into clinicaltrials.gov. And we get a lot of requests, in fact, for other possible indications. Right now, we're focused on the two genetic indications that we're most comfortable with, but we're supporting some other efforts, which could potentially become sponsored efforts if they show -- if there's a reason to invest.

With KRN23, the TIO and XLH, are really the important ones. There is autosomal recessive and autosomal dominant types of hypophosphatemia, which are also associated with elevated FTF 23. They're relatively smaller indications, and we're at the point where we're not actively pursuing them, don't think it adds to the story.

I think the TIO was important to do because there were a lot of patients in very severe condition. And we were getting a lot of compassionate use requests, and we felt like that was a disease area where we felt there it was distinctly different and perhaps an area we could show substantial benefit if the treatment was effective. So those are those two.

For some of the other programs like an enzyme therapy for MPS7, we're not anticipating a large number of major markets for MPS7 enzyme, but if you found one, let us know. But that's a small population, but we think are a really important disease stage. So we'll continue to do some products that are like that that don't have large secondary indications.

I think that's -- probably KRN23 and Triheptanoin are probably the most important ones with regard to that. I think right now, also our effort is really pulling in the new pipeline, the next INDs. And I think we're seeing some really interesting things, and I feel pretty good about us building our a very nice early stage pipeline and [doubt] that we refill the pipes as we move forward.

Thank you.

Great. Well there are no additional questions, I guess, so that concludes the call today. A replay of this call will be available shortly by webcast and phone. If you have any other questions off-line, feel free to contact us at 844-758-7273 or by email at ir@ultragenyx.com. Thanks, everyone, for joining us.

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