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Ultragenyx Pharmaceutical Inc (RARE -0.13%)
Q2Â 2019 Earnings Call
Aug 1, 2019, 5:00 p.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good afternoon, ladies and gentlemen, and welcome to the Ultragenyx Second Quarter 2019 Financial Results and Corporate Update.
[Operator Instructions] I would now like to turn the conference over to your host, Ms. Danielle Keatley, you may begin your conference.
Danielle Keatley -- Senior Director of Investor Relations and Corporate Communications
Good afternoon and welcome to the Ultragenyx Pharmaceutical Financial Results and Corporate Update Conference Call for the Second Quarter 2019. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. I'm Danielle Keatley, Senior Director of Investor Relations and Corporate Communications.
With me today are Emil Kakkis, Chief Executive Officer and President; Shalini Sharp, Chief Financial Officer; Vlad Hogenhuis, Chief Operating Officer; and Camille Bedrosian, Chief Medical 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 1995, including but not limited to the types of statements identified as forward looking in our quarterly report on Form 10-Q that will was filed on May 7, 2019. Our quarterly report and Form 10-Q that will be filed soon and our subsequent periodic reports filed with the SEC, which all will be available on our website in the Investor section.
These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statement. For 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'll now turn the call over to Emil.
Emil D. Kakkis -- Chief Executive Officer and President
Good afternoon everyone, and thank you for joining us. I'll start today by providing some brief introductory remarks and before turning the call over to Vlad, who will discuss the commercial performance in the second quarter of 2019. Next, Shalini will update you on the second quarter financial results. Wlad and Camille will then discuss the latest progress across our clinical programs, and I'll come back and discuss the outlook for the rest of the year.
Our commercial momentum continues to grow in the second quarter of this year with strong launch progress in both Crysvita and Mepsevii in three major territories -- throughout the world. Yesterday, we submitted our new drug application for UX007 or triheptanoin for the treatment of long chain fatty acid oxidation disorders. We have relentlessly focused on advancing UX007 through the clinic and into regulatory review, in order to get this therapy to patients as quickly as possible. For our gene therapy platform, we continue to move our two clinical programs forward this quarter, one for the treatment of ornithine transcarbamylase deficiency and the other for Glycogen Storage Disease Type 1a.
Importantly, we recently solidified our mRNA platform by expanding our collaboration and license agreement with Arcturus. The collaboration now includes up to 12 rare disease targets and provides a greater opportunities to treat more diseases with mRNA, siRNA and DNA therapeutics. We've seen promising results from this partnership so far. Our lead mRNA program UX053 for the treatment of Glycogen Storage Disease Type III or GST 3 is expect to advance to IND in 2020. In addition to our mRNA program with GST 3, we have two other pre-clinical programs moving ahead toward IND filings. These include our gene therapy program for Wilson's disease and our dual-trigger pro-drug for Creatine Transporter Deficiency.
Now I'll turn the call over to Vlad to walk you through the commercial performance through the second quarter of the year.
Wladimir Hogenhuis -- Chief Operating Officer
Thank you, Emil and good afternoon everyone. The second quarter of 2019 was a strong quarter for Crysvita in the United States. Since our launch in April of 2018, we've received approximately 1,300 completed start forms from treating physicians. The continued growth in the number of completed start forms this quarter is in line with the prior quarter. The split among pediatric and adult patients continue to hold steady with roughly 60% pediatric patients and 40% adult patients. Approximately 580 unique physicians have now prescribed Crysvita. As first time prescribers gain more experience with the therapy and the reimbursement process. We're seeing these prescriber wide prescriptions for multiple patients. We are encouraged that these numbers continue to grow with more than a third of prescribers today writing prescriptions for more than one patient.
Earlier this year, we received a specific J code for Crysvita. This helps simplify the buy-and-bill process, especially for Medicare and Medicaid patients. As a result of the J code and increasing number of state Medicaid policy, the payer mix continues to shift. We currently have approximately 40% government and other payers and 60% private payers to date. We have nearly full coverage of lives within the U.S. at this point. Additional payers without formal policies are approving Crysvita on a case-by-case basis.
With this broad coverage across all payer types, we now have approximately 960 patients on reimburse commercial therapy. Earlier this year we implemented easy access to confirmatory genetic testing, independent genetic counseling, and pedigree analysis programs. These initiatives have improved a process, but then finding more patients with a confirmed diagnosis and converting patients to reimburse therapy. Consequently, we had a substantial increase in number of patients who began reimbursed therapy in the second quarter. We launched Crysvita in Canada earlier this year, and we're seeing strong interests and uptake among patients with private insurance. We're also pursuing public reimbursement in Canada, which can take up to two years.
Moving to Latin America, we will see the approval of Crysvita in Brazil earlier this year, where we are continuing to pursue pricing and reimbursement. We also expect regulatory decisions from the Chile and Colombia and the Mexican health authorities this year and next. Reimbursement decision in all of these markets can take a few years. And in the meantime, we continue to respond to name patients request.
Briefly turning to Mepsevii. This therapy is approved in the United States, Europe, and Brazil, and the launch continues to go well. In order to expand availability of Mepsevii to more patients around the world, we're continuing reimbursement discussions with various government health authorities, and we expect additional regulatory decisions in Mexico, Colombia and Chile this year and next.
With that I'll turn the call to Shalini, who'll provide a financial update.
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Thank you, Vlad, and good afternoon everyone. We issued a press release earlier today that included a financial update, which I will briefly summarize. Total revenue for the three months ending June 30, 2019 was $24.1 million.
For the quarter ended June 30, 2019 Ultragenyx recognized total Crysvita revenue of $20.2 million. This includes $17.3 million in collaboration revenue in the North American profit share territory and $1.9 million in royalty revenue from our partner Kyowa Kirin or KKC [Phonetic], sales in the European territory. Net products revenue for Crysvita and other regions, totaled $1 million. Top line worldwide revenue of Crysvita totaled approximately $73.3 million. This represents the total sales across North America, Europe and Latin America, a portion of which are shared with KKC. Mepsevii product revenue for the second quarter of 2019 was $3.2 million and UX007 named patient revenue was $0.6 million.
We also recognized $0.1 million in revenue from our research agreement with Bayer. As we've stated previously, we continue to expect revenues from this agreement to be minimal going forward. We are continuing to gain commercial experience with both Crysvita and Mepsevii and will not be providing financial guidance at this time. We have provided launch metrics, including patients on reimbursed therapy, growth in start forms and unique prescribers to help characterize the strength and momentum of our launch. We plan to provide this level of granularity only in the early quarters of launch and we are evaluating the appropriate time to shift specific revenue guidance as we gain experience with the launches in multiple territories.
Our total operating expenses were $136.6 million for the second quarter of 2019. Our research and development costs were $96 million, including a $15.6 million research and development expense from Arcturus collaboration amendment. We expect our R&D costs to continue increasing over time as we advance additional product candidates from pre-clinical development into early and pivotal clinical studies. We expect SG&A to increase over time as we support our commercial programs in multiple geographies. We expect the split of R&D versus SG&A expense to remain fairly consistent. Net loss for the second quarter of 2019 was $99.2 million or $1.72 per share, basic and diluted, compared with net loss of $52.7 million or $1.06 per share basic and diluted for the second quarter of 2018.
The loss for the second quarter of 2019 includes the $15.6 million R&D expense related to the Arcturus amendment and a $9.8 million unrealized gain from the fair value adjustment on the investment in the Arcturus equity. Unlike the R&D expense, the change in the fair value of the investment in Arcturus equity, pursuant to this amendment, will be reflected in future periods. Recall that the loss for the second quarter of 2018 includes a $40.3 million gain from Ultragenyx's portion of the sale of the priority review voucher received with the Crysvita FDA approval.
For the first half of 2019, cash used in operations was $184.8 million, which includes the $15.6 million R&D expense from the Arcturus transaction and also includes adjustment for significant non-cash charges, such as stock-based compensation expense of $42.4 million, $4.2 million in depreciation and amortization and $0.6 million in non-cash foreign currency remeasurement, due to exchange rate fluctuations. This is compared to $165.6 million for the same period in 2018, which included adjustment for significant non-cash charges, including stock-based compensation expense of $38.4 million; $12.2 million in depreciation and amortization; and $5.8 million in non-cash foreign currency remeasurement losses resulting from the restructuring of some of our foreign subsidiaries and fluctuations of exchange rates.
We ended the second quarter of 2019 with $618.3 million in cash, cash equivalents and available for sale investments which factors in the $30 million paid in the Arcturus collaboration agreement. We believe our cash resources should be sufficient to continue to support the initial years of launch for Crysvita and Mepsevii and allow us to continue to build and advance our clinical and translational research program pipeline.
I would now like to turn the call over to Camille, who will provide an update on our clinical programs.
Camille Bedrosian -- Chief Medical Officer and Executive Vice President
Thank you, Shalini. And I also wish everyone a good afternoon. Starting with UX007 for long-chain fatty acid oxidation disorders or LC-FAOD, these series disorders have unpredictable and precipitous consequences for patients that can lead to metabolic crises and frequent hospitalizations. There is a high mortality right rate despite newborn screening and current management with medium chain triglyceride or MCT oil. Therefore, we believe the new treatments are urgently needed for patients with LC-FAOD.
Yesterday, the team completed a significant step toward our goal of bringing UX007 or triheptanoin therapy to patients. We submitted our new drug application to the FDA. The submission is supported by a comprehensive package with data from a broad range of over 150 patients, the majority of whom have been treated over a long period of time. The submission includes results from, the company sponsored Phase 2 study, the long-term efficacy and safety extension study, which includes 20 patients previously naive to UX007. Our retrospective medical review -- record review of compassionate use patients expanded access data and the randomized control investigator-sponsored study showing the impact of triheptanoin on cardiac function. Earlier this year, the FDA granted rare pediatric designation and Fast Track designation for UX007, which enables eligibility for priority review. Now that we have submitted the application, we expect to hear back from the FDA on submission acceptance and priority review designation within 60 days.
Moving to DTX 301, our gene therapy program for ornithine transcarbamylase deficiency or OTC deficiency. OTC deficiency is an excellent urea cycle disorders, that limits the body's ability to metabolize ammonia. Patients with OTC deficiency buildup excessive amounts of ammonia in their blood and can quickly deteriorate into full metabolic crisis, suffering from neurological deficits and other toxicities leading to hospitalizations, coma, and even death. We previously reported data from the first two dosing cohorts of the OTC-study. And in these cohorts we had two responders who had have since maintain normalized urea genesis levels for 78 and 52 weeks, respectively, continue to tolerate the discontinuation of their ammonia scavenger medications, liberalize their diet to include more protein and manage through infections without experiencing rises in their ammonia levels.
We have not seen any infusion-related adverse events or treatment-related serious adverse events. These data suggest so far, then a metabolic cure is possible for OTC deficiency with this gene therapy. We are currently evaluating DTX 301 at a dose of 1/10 [Phonetic] gene copies per kilogram and we will provide an update on the program in the third quarter.
DTX 401, our gene therapy program in Glycogen Storage Disease Type 1a or GSD1a continues to progress as well. GSD1a is caused by a defective gene for the enzyme glucose-6-phosphatase alpha resulting in the inability to allow the liver to release glucose into circulation. This could potentially lead to severe hypoglycemia during fasting or during times of increased metabolic stress, such as infection. We previously provided 24-week data for the three patients in the lowest dose cohort of [Indecipherable] gene copies per kilogram. At this time point, all patients showed durable clinical responses and maintained or increased their time to hypoglycemia in a controlled fasting setting. Importantly, all three patients have sustained their reductions in cornstarch compared to baseline with reductions of 86, 46 and 73% at 36 weeks, which demonstrates further improvement in glucose metabolism in the liver. We have moved to the second dose cohort and are evaluating DTX 401 at a dose of 6E12 [Phonetic] gene copies per kilogram. We plan to provide an update on this program in the third quarter of this year as well.
I will now turn the call back to Emil.
Emil D. Kakkis -- Chief Executive Officer and President
Thank you Camielle. I'll spend a few minutes discussing a number of important milestones in the coming months, that will continue to drive our progress, and then we can move to the Q&A. For Crysvita, we expect to see its continued strong growth start forms, reimburse patients and prescribers in our U.S. launch and will continue to expand our reach with the recent Canadian launch in named-patient sales and regulatory decisions in Latin America. As the product launch proceed past U.S. alone, we expect our efforts to file and gain approval early -- those territories will contribute to a broadening base of Crysvita revenue for the Company over the coming years.
For UX007, we anticipate hearing back from FDA on the submission acceptance and review designation. In the next 60 days, we will continue to work with the FDA throughout the process and ultimately believe this therapy could offer a meaningful treatment option for patients with long-chain fatty acid oxidation defects. Moving to the gene therapy programs, our two programs in Glycogen Storage Disease Type Ia and ornithine transcarbamylase deficiency continue to progress and we will provide an update on both clinical programs in the third quarter.
Finally, for the pre-clinical pipeline, we're continuing to advance three of our pre-clinical programs and assemble data packages and we are on track to submit 3 INDs in 2020. To summarize briefly our launch momentum with our first two approved therapies continues to grow and UX007 is not far behind. We have fulfilled -- we've refilled our pipeline with two clinical stage gene therapy programs and three promising preclinical stage program and all nearing IND. We have been successful and rapidly developing multiple rare disease therapies for patients who do not have a good treatment option are well poised to continue to deliver. There are few companies, there are very few companies who have completed four successful clinical programs in the last five years since IPO, and also filed three BLAs or NDAs in this timeframe.
Our ability to develop, obtain approval and commercialize globally puts us in a unique category in terms of skills and efficiencies as a rare disease company. The catalyst we had on gene therapy, new product filings, regulatory progress and commercialization will make for a productive year.
Let's move to your questions. Operator, can you please provide the instructions for the Q&A portion of the call.
Questions and Answers:
Operator
Absolutely. [Operator Instructions] Your first question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Hi, good afternoon. Thanks for taking my questions. Emil just wanted to ask you about the readouts for 301 and 401 in the higher dose cohorts. So if the -- data for both are positive, what would be the next steps that you would take?
Emil D. Kakkis -- Chief Executive Officer and President
Well, both protocols for 301 and 401 define that if we reached the dose that we're going to continue, we would then add another cohort 3 patients at that dose. And then with that information we'd be ready to plan Phase 3. We are also looking at other things we might do in enhancing the treatment and we will talk more about as we move ahead. But we would first want to confirm, whatever we find in that dose cohort with another few patients, -- before we'd want to proceed to FDA and talk about a Phase 3 program for both studies -- both program.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
And is it your intention that if the data look positive for both to move both forward? Or there are any constraints in terms of how much these would cost, which you have to choose one over the other?
Emil D. Kakkis -- Chief Executive Officer and President
At this point, we are planning, our plan include putting both products in the Phase 3 and that's we're planning from a CMC perspective, as well as the clinical development perspective.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Okay. Thanks.
Operator
Your second question comes from the line of Maury Raycroft from Jefferies. Your line is now open.
Maury Raycroft -- Jefferies LLC -- Analyst
Hi, everyone. Congrats on the progress and thanks for taking my questions. My comment was -- my question was just on the named-patient requests in Latin America that you've received so far. And if you can provide any details on how the named-patient pricing will work and the revenue contribution from this region over the next few quarters?
Emil D. Kakkis -- Chief Executive Officer and President
I think it's important, I think we've already been receiving and putting some revenue from named-patient request that we have been responding to. I'll let of Vlad provide perhaps a little more detail on what's going on in South America.
Wladimir Hogenhuis -- Chief Operating Officer
Thank you, Emil. So we're getting named-patients request in a number of countries, Argentina, Colombia and Brazil. We are processing -- requests and submitting them with the appropriate documentation, with relevant healthcare authorities. And once were invoiced, we actually recognize the revenue in Brazil. To give you a little bit of color, the patients have to go through the legal system to get an injunction for the product and that process is going. It's of course and we're looking forward to helping all of patients in Latin America with named-patient requests.
Maury Raycroft -- Jefferies LLC -- Analyst
Got it, OK. And then just a question on the gene therapy program, so with the guidance for 3Q we've noticed that there are two titles at the SSIEM [Phonetic] Conference. Just wondering if, if you can provide any more specifics on whether the data would be top line around that conference?
Wladimir Hogenhuis -- Chief Operating Officer
We haven't planned, what would be precisely shown at the conference yet, but certainly it is possible, but we haven't yet prescribed what will be in the conferences. I think the abstract include existing data.
Maury Raycroft -- Jefferies LLC -- Analyst
Got it. Okay, thank you very much.
Operator
Your next question comes from the line of Gena Wang from Barclays. Your line is now open.
Gena Wang -- Barclays -- Analyst
Thank you for taking my questions. Maybe just follow Maury's questions regarding Latin America, how soon do you think we will get the meaningful revenue contribution, the commercial patients -- the reimbursement process?
Emil D. Kakkis -- Chief Executive Officer and President
Well each country, as Vlad noted was different. In Argentina, unlike in the past, they have a new law that allows for named-patient reimbursement. So we actually start getting Argentina first. We've gotten some from Colombia. In Brazil, things have changed and we have filed and gotten approval there and what Vlad just talked about a moment ago was, in that process patients have to request through the legal process, their constitutional right to get treated. And there are a number of patients seeking that, that process takes time, once some patients get through that process, then it may go faster than. But Brazil have that step and that can take some time, but there are substantial number of patients seeking treatment in Brazil and there -- I was down there myself for conferences and meetings with investigators and there is a lot of interest in Brazil in this treatment and anticipation of being able to put their patients on itself. We're excited to see this process move ahead.
Vlad, maybe you can also tell us, tell them about the reimbursement in Brazil and the timeline for that.
Wladimir Hogenhuis -- Chief Operating Officer
Sure, so as you don't know, we got regulatory approval in March in Brazil. We are now proceeding to getting pricing and reimbursement approval. We expect that by the end of 4Q of this year. Once that's complete we will start to process of reimbursement and that can take between two and five years in Brazil. And we're preparing for submitting that dose --. But in meantime as Emil said we're getting lots of interest from patients who want to evaluate our Crysvita slide for XLH. And we're taking all of these request and supporting them appropriately up to getting reimbursed by the Ministry of Health, which we hope to see accelerate soon.
Gena Wang -- Barclays -- Analyst
Okay, thank you. And regarding the U.S. revenue just based on my rough calculation and the U.S. is roughly the revenue is about $52 million and just wanted to see if they're in-line with your numbers for Crysvita? And also for the 40% of the adult patient, just wondering how much -- how many of these patients like the percentage that through the new patient resources versus existing family tree of the pediatric patients?
Emil D. Kakkis -- Chief Executive Officer and President
Right, several questions there. I would just answer the second part, I don't think we could know for sure what keen to family trees and we wouldn't be able to provide that detail on the link between patients. We definitely know there is some families are getting on treatment where mom and kids are going on treatment together. But we are, I couldn't give you that information at this point, I thought perhaps Shalini is closest to the finance numbers could put forth what we've put out on the revenue.
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Sure. Thanks for the question, Gena. And as you may have noticed Kyowa Kirin does not break down the revenue by territory. So that's not disclosed by them specifically. But what we disclose is at this for this quarter our share of the collaboration revenue and the profit share territory in North America is $17.2 million. The royalty revenue in Europe, which is an up to 10% royalty rate is $1.9 million. So those are all the publicly disclosed numbers that we can discuss at this time.
Gena Wang -- Barclays -- Analyst
Okay. Thank you.
Operator
Your next question comes from the line of Joon Lee from SunTrust Robinson. Your line is now open.
Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst
Hey, thank you for taking this question. And this is a Fang on for Joon. Quick question, on the 301 and I remember you mentioned at one of the conference that, there is some gender differences may constitute a variability of the response. Maybe can you just elaborate on that, what are the evidence you have seen? Is it mainly from animals or it comes from pre-clinical evidence as well? Would do you see any evidence from other clinical studies which supporting their gender differences in terms of response to gene therapy? And I have a follow-up.
Emil D. Kakkis -- Chief Executive Officer and President
Yes. Thank you. So we observed is one possible explanation for our different response to different patients in the early cohorts could be a gender, and we have not proven that. There is examples in the literature, in animal models of differences in the gender efficiency particularly with females being more resistant. And there is some evidence that relates to female [Indecipherable] and their effect on immunity, that may be enhancing immunity. We don't have evidences as that truthful was happening in our patients that was one possibility. We believe though that with increasing the dose we are able to overcome in a immunity and be able to provide the response. We're looking for in female patients too. We're certainly looking at all possible angles on how to manage that. The other clinical programs, many of those programs have been excellent that have released and therefore you're not seeing a male, female difference, but it is something that's been known before and something that I think will have to be considered in gene therapy.
Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst
Great. That's very helpful. And the second question is on 401. And I think you also mentioned that one patient, -- if there is a reduction in starch consumption and then patient going to produce more insulin, and insulin in-turn going to suppress transient expression as some degree. And just maybe help us understand that, how insulin going to suppress transient expression? I think you mentioned about the normal promoter what you used for the -- for your transgene, that's why there is probably a [Indecipherable] loop where it contribute to that. Maybe you can help us understand that will be more -- could be helpful. Thanks.
Emil D. Kakkis -- Chief Executive Officer and President
Sure. So we believe that the control of glucose 6 phosphate needs to respond to normal physiologic signal, like insulin or glucagon, the things that control glucose in your body. And so the design is that concluded our three kilometers of the promoter region, which includes elements that respond to both insulin, glucagon as well as to steroids or stress responses as well. All of those will give the patient, the potential to increase transgene expression under the condition that would normally increase glucose-6-phosphatase. We think that would provide an optimal phenotype rather than fourth expression of that enzyme. We know that insulin will suppress the promoter, we've shown that in-vitro. But all we need to do in a patient on the starch is need to wane their starch and let their insulin levels come down with the expression of the gene, to come back to normal. And that process has received in the first three patients. And as they reduced their starch, they've clearly been able to maintain their glucose. And as you heard now, one is at 86% reduction, one is in the 70% reduction. Really all three are down into a relatively small amount of storage, because the second patient had a lower reduction, actually started at a lower number to begin with.
So actually all that are relatively low amount of starch now. So I think what that shows, as long as we keep ramping back, their starch, they come internal and manage their glucose with the new transgene provided. So we're confident as we look forward this program that's waning on the starch maybe part of how we get them to switch their metabolism away from starch, insulin dependent system to one that is based on the new enzyme we provided through the gene therapy.
Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst
Okay. That's very helpful. Thank you so much.
Operator
Your next question comes from the line of Arlinda Lee from Canaccord. Your line is now open.
Arlinda Lee -- Canaccord Genuity -- Analyst
Hi guys, thanks for taking my question. I'm also curious about the upcoming data set with 301 and 401. I'm curious, Emil you talked about potentially looking at different dosing schemes. I'm kind of wondering what you're looking to do with those dosing schemes? And then as well for the 401, what kind of, I mean all these patients in the first cohort seem to have had an effect. Curious as to what do you think the threshold for expanding that particular cohort would be? Thank you.
Emil D. Kakkis -- Chief Executive Officer and President
Sure. So, in 301, we talked about dose is one lever and we've gotten now to the e13 level. And we'll put out our data when we get enough data on the patients, to -- to make a conclusion. Our expectation is if that level should be enough. What we've talked about possibly adding prophylactic steroids as another lever in order to enhance the efficacy, we see, and perhaps improve that if necessary. So there is no option we have that dose is nothing [Indecipherable] in terms of what we might do. And we'll see what the results look like and make a decision, but I do want to do in our program start, is to get more experimental and actually study what we need to study in order to get the right answer. Could these decisions are affecting patients their whole life, and we need to make them in the right way with comparative treatment approaches.
For the 401 question we've -- the three patients have gotten pretty close to complete metabolic control. And that included other findings that were discussed at the Analyst Day in detail, which we haven't reiterated now. We're looking to see if we can continue that as the next dose level and try to understand as that level of efficacy what is achievable or is there a higher level achievable. But it is actually pretty good at the first cohort level, and some of that, the question was that, that enough. And I think it could be enough, but I also think it's -- it moves up to explore the second dose level to ensure that if it were different or better we know.
I do think it takes time to see the result, because of the need to wean the start and see how they respond to that. But the potential is that the 6e12 dose will be sufficient or high enough to achieve the maximal effect, and we'll be able to proceed from there. And we'll put out that data later this quarter, third quarter.
Arlinda Lee -- Canaccord Genuity -- Analyst
Thank you.
Operator
Your next question comes from the line of Joseph Schwartz from SVB Leerink. Your line is now open.
Unidentified Participant
Hi, I'm [Indecipherable] dialing in for Joe. Thanks for taking our questions. I was wondering if I could ask a question on DTX 301. Specifically, how does the third dosing tested in humans compared to doses tested in pre-clinical models such as mice and what percent of the -- what percent of normal gene expression was achieved in mice, and two different OTC deficient patients need different levels of correction based on mutation. And I have a follow up.
Emil D. Kakkis -- Chief Executive Officer and President
Very good. The mouse dosing is a little difficult to translate because mice are much more easily treated with AAV vectors. So the dosing in mice is 110th of 140th [Indecipherable] using in humans, just to be clear. So the exact way to translate the doses is hard, but the e13 should be a range translate the mouse that should be a fully therapeutic. But what I would say to you that in the mouse, it's easily achievable to reach our 100% [Indecipherable] cured, but in humans and animal primates, the number is significantly less even at higher doses. The cheaper we have to get in this program, is to get to what we think is about 80% of normal ureagenesis, which is really maybe a doubling of the amount of ureagenesis they have.
So they may have, let's say, 3% to 5% of normal to be these types of patients, and we need to get them into more like the 8% to 10% range. So we don't have to get them to 100% to achieve a level of enzyme sufficient to give them normal ureagenesis. In the first -two patients that did reach around 120% of normal ureagenesis, that doesn't mean their enzyme will hold 120%, it means their ability to convert urea is now 100 times a normal. But that means their level is probably in the 10% or 15% of normal range in the cells that have the gene and they are able to convert enough ammonia to give them what is equivalent to normal ureagenesis or sufficiently normal ureagenesis.
So to be clear, we're looking at a relatively small increase. But in the mouse it's -- at these dose levels it's easy to get to 100%. But we know in animal primates, in humans are different and more resistant to AAV. And that is what everyone in the gene therapy space is working to overcome the humans ability to resist these vector as compared to what mice were a pretty easy going with regard to AAV.
Unidentified Participant
Okay, great. Thank you for the clarification. And my next question has to do with UX007. I was wondering if you could provide some color on your --on your commercialization strategies, assuming the drug is approved. Given that your field force is currently working with physicians and patients with the different treatment base, with Crysvita and Mepsevii.
Emil D. Kakkis -- Chief Executive Officer and President
Yeah. So the type of doctors that treat Crysvita are some -- are different, some endocrinologists actually that do handle metabolic disorders too, it depends on the institution. We're very familiar with the launch of products into the metabolic, generic [Indecipherable] have involved in multiple five or six launches. There is around 160, 200 centers that are where these patients are concentrated and managed and a relatively smaller team can actually manage that. And the commercial team will be looking at the options, whether it's how leverage existing team. We already have a metabolic in that MSL team and so forth. But I think there is some time for us to figure out the best way to launch. But we wouldn't want to impair the Crysvita launch. At the same time we want to make sure we resourcing this launch. But because it's a relatively smaller number of targets compared to the number of targets we're dealing with in Crysvita, we don't think we'll need anywhere near as large a team as we are with Crysvita, given the size of the product and the number of doctors we have to see.
Unidentified Participant
Okay, great. Thank you very much.
Operator
Your next question comes from the line of Vincent Chen from Bernstein. Your line is now open.
Vincent Chen -- Bernstein -- Analyst
Thank you very much for taking the question. Another one, revisiting the gene therapy programs, and especially DTX 301, you previously alluded that you've been going back to result and trying to assess what's driving some of the heterogeneity in the results. I was wondering what the latest thinking on that is and what are some of the leading hypothesis? And then as a corollary related to some of the earlier questions and commentary, if the updated data in the third quarter continues to show a lot of heterogeneity, what would be the range of potential steps in addressing this? I know you've alluded to increasing the dose in prophylactic steroids, but help me understand the range, might you consider something to suppress B cells or other elements of the immune system. What are the range of levers that you could reach for appending your analysis of the drivers of their ability?
Emil D. Kakkis -- Chief Executive Officer and President
Very good. So with regard to the first question I don't think we have any new hypotheses on what's going on. I think innate immunity which could be gender dependent is clearly one of the factors that is the source of variation in all gene-therapy programs. And it still remains to be one of the possibilities. Most of the time people been able to overcome that with dose and I hope that e13 would be the dose that does that, and we'll provide that data later this quarter. One of the things we've been considering from the beginning, when you think about any immunity is how to suppress it, and prophylactic steroids have been shown to improve the transduction by AAV. We've seen it in non-human primate studies. We've done, I think is also from other companies' products that have hired it both ways, with and without prophylactic steroids that there is clearly a significant impact on the productivity of expression using prophylactic steroids. So I think it's a natural thing to add-on and a very simple thing to add-on, if it can enhance the expression a couple of fold it's needed. And even if we are achieving normal levels, if adding steroids gave you another twofold boost, just a few weeks of steroids. It's worth doing whether even if you're hitting 100% normal because these long-term benefit of enhancing their gene therapy, the prevalence of cells are expressing I think is important. So we are looking at that as something we might do here in the Phase 2 program to tell us whether that might be an added benefit, relatively simply.
We're currently not looking at other types of targeted drugs' I think there is a lot out there. It takes you into a much more difficult area, and I don't think it's necessary. Our focus a little bit less on adaptive immunity, you mentioned B cells and a lot more on innate immunity, as being the kind of the core [Indecipherable], because we're not seeing transgene directed antibodies or immuno responses, we're seeing the question of getting the expression initially. If you're seeing antibodies to the transient, then you might want to think about things that affect that part of immunity. So right now focus on suppressing innate immunity, enhancing through dose and we might look at prophylactic steroids as an easy option to potentially boost compression.
Vincent Chen -- Bernstein -- Analyst
Great. Thank you very much.
Operator
Thanks. Next question comes from the line of Laura Chico from Wedbush Sec. Your line is now open.
Laura Chico -- Wedbush Securities -- Analyst
Hello. Good afternoon and thanks for taking the questions. I was wondering if we could go back to XLH for a moment and your earlier comments around the genetic testing, I'm just curious if you've had any sense as to whether that 12,000 figure you put out there in terms of the population, perhaps how that might shift with the implementation of genetic testing? And then I have a quick follow-up for you.
Emil D. Kakkis -- Chief Executive Officer and President
Well, we haven't put out results for inject testing program so far, but I think among clinically diagnosed XLH patient we're seeing very high frequency of confirmed XLH. And so we feel comfortable that the clinical diagnostic prevalence numbers are accurate, and we wouldn't think the testing would alter those numbers at this point in time.
Laura Chico -- Wedbush Securities -- Analyst
Okay, got it. And then I guess kind of related to XLH, wondering now as you've had a few more quarters kind of under your belt here. Can you comment at all perhaps on persistency and compliance rates as more patients have titrated up and are there any differences that you're observing across the pediatric versus adult patients? Thanks.
Emil D. Kakkis -- Chief Executive Officer and President
We haven't yet put out the formal persist compliance rates, and we don't -- I don't actually have them. But what I can say is that pediatric patients who are in the trials have essentially all stayed on drug and we haven't lost anyone. So I'm aware of -- so I certainly in some of the population resistant -- among the adults there were a few from the trial who may not have continued. But it's been relatively good, and our confidence so far is that persist the compliance has been very good. And it's not, we don't think a source of problems in the program at this point.
Laura Chico -- Wedbush Securities -- Analyst
Thanks very much.
Operator
Your next question comes from Yigal Nochomovitz from Citigroup. Your line is now open.
Yigal Nochomovitz -- Citigroup -- Analyst
Hi Emil and Shalini, thanks for taking the questions. I just wanted to make sure I understand properly some of the trends, quarter-over-quarter from 2Q to 3Q. So there was a -- approximately 30% increase in patients reimbursed in the U.S., but you saw a much higher 45% increase in collaboration and profit share in North America. And as much far as you understand there was no price growth and you just mentioned earlier that -- there was a consistent 60-40 split on the patient mix for pediatrics and adults. So I just trying to get an understanding of what the discrepancy is? Is it related to maybe a skewing in the cadence of patients in the quarter or not accounting for the growth in the Canadian patients or potentially a shift in the payer mix? If you could just provide some insight into -- how that aligns up? Thanks.
Emil D. Kakkis -- Chief Executive Officer and President
Sure, we can do that. I do think, one of the thing that did change is that the, we were getting more patients reimbursed, compared to -- compared to the rate of start form generation, we definitely close the gap on the reimbursed patients that definitely was a difference in the quarter. I don't have enough feel for the numbers, maybe Shalini you can provide some input on the question of those differences?
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Yeah, no, it's a great question. And I think half the story is probably the increase in the reimbursed patients versus the start forms that proportion, that reimbursed is higher than in prior quarters. And secondly then you're absolutely right about Canada, actually that the start form data that we provide you is U.S. only, whereas obviously the North American profit share revenue includes Canada as well. So those are the two key explanations.
Emil D. Kakkis -- Chief Executive Officer and President
And we do have patients on reimbursed therapy in Canada, who have private insurance, and that's continuing to grow.
Yigal Nochomovitz -- Citigroup -- Analyst
Okay. So the profit -- the profit share calculation, I know you haven't -- gotten into the details on that. But that's constant. It's not as though you're getting a better a higher margin -- with a higher base on revenue?
Emil D. Kakkis -- Chief Executive Officer and President
No.
Yigal Nochomovitz -- Citigroup -- Analyst
Right. Okay. And then the other question I had, you mentioned the prophylactic steroids -- and we noticed on clinic trials, at least for 301, you have at least publicly disclosed experimental cohort with the prophylactic regimen of prednisone. And we were just wondering whether that same plan exists for 401 as we hadn't seen that particular detail posted for 401 yet. Thanks.
Emil D. Kakkis -- Chief Executive Officer and President
Well, we are considering the weather, [Indecipherable] could enhance the expression at any dose level based on data we've seen in animals, as well as other people see in the clinic. So we're considering the 401. For 401, the use of steroids has some complexities because of how it affects their glucose metabolism. So we're working through that discussion, we could potentially add it, we haven't made that final decision. For 301, we felt it was worth just doing it to verify, if we got a bump with steroids for something so simple, it would be worth capturing, it help the prevalence and enhance the overall expression we see.
Yigal Nochomovitz -- Citigroup -- Analyst
Got it. All right. Thank you very much.
Operator
And your next question comes from the line of Jeff Hung from Morgan Stanley. Your line is now open.
Jeffrey Hung -- Morgan Stanley -- Research Analyst
Thanks for taking the questions. If I can dig a little bit more on the pricing approval in Brazil, can you talk about the steps that remain outstanding ahead of the formal reimbursement dossier?
Wladimir Hogenhuis -- Chief Operating Officer
Sure, I'll start with, and Vlad finish. So to be clear, in Brazil, things have changed over time. The Brazilian government wants and orders you named-patient or legal process reimbursements, they want to see the drug approved. This is partly why we filed immediately rather than doing that process in the pre-approval setting. So we filed it get approved, which allows you enable to do the named-patient response where the patient request therapy and does this legal process to get access. That process starts perhaps two or three cases get taken through. And then the other cases, will get adjudicated more promptly than, then the first few. So we're in the middle of that process right now and have quite a few Brazilian patients who were queued up and in that process.
And I'll let Vlad talk a little bit about the other process. There are several steps and the exact amount of time is unknown. And of course, in addition to the normal process we are going to look to negotiate an access program, if we can, to go faster than the usual process. But maybe Vlad and tell you what the -- just remind me briefly again what that process was the -- normal commercial reimbursement process.
So after approval, we are submitting a pricing approval process. So we submitted that report and we expect to hear back from the Brazilian Ministry of Health around November-December. Once that is completed, we expect to price close to the U.S. base. We will be submitting a reimbursement dossier in 1Q 2020. And the typical time for that to get respond that can vary anywhere between five to two years, closer to five. Their opportunities that to actually do a public-private partnership. We'll be exploring those in 1Q, after we receive the pricing approval. But I'd like to add though is that we have a very experienced team in Brazil, who has done many named-patient programs for other companies, so they are well versed in getting these requests from the physicians compiling all the information required by the Ministry of Health and ensuring that patients follow the appropriate values to the legal system. So they are well experienced and we're now kind of waiting for these patients to get through, the legal system up to the Ministry of Health, where we will see the first unnamed [Phonetic] patient sales materializing.
Jeffrey Hung -- Morgan Stanley -- Research Analyst
Great. Thanks. And then Shalini you mentioned in the initial part of launches, you've been providing metrics rather than guidance. Can you remind us how you're thinking about an appropriate time to change to guidance. Is it a timing thing after certain number of quarters, are you waiting for a certain amount of sales in a given quarter? Thanks.
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Yeah, that's a good question, we have studied the analogous products and other rare disease launches in recent years, and there is a wide range of practice around when to provide guidance. And because we have sales not only in North America, but also in other territories. We're in various stages of launch, depending on which product in which territory. And to top of that, with Crysvita we also have a collaboration with Kyowa Kirin. So we have to align with them on when they would like to provide guidance. So those are all the kinds of things we'll be considering, so once we have a further level of maturity for these products in more than one market and agreement with our partner, then we'll be able to provide guidance to you.
Jeffrey Hung -- Morgan Stanley -- Research Analyst
Great. Thank you.
Operator
Your next question comes from the line of Chris Raymond from Piper Jaffray your line is now open.
Nicole Gabreski -- Piper Jaffray -- Analyst
Hi, this is Nicole Gabreski on for Chris. Thanks for taking the question. So just on gene therapy manufacturing for HEK293 and HeLa set up. I was just wondering within your centers of excellence, are these two manufacturing platform is being used within the same facilities? And if so, could you just give us a bit of color as to the safety precautions that you take to limit the risk of adenovirus contamination from the Kyowa platform?
Emil D. Kakkis -- Chief Executive Officer and President
Thank you for your question. Currently, the 393 cell-based contract manufacturing we are doing in the different places from where we're doing the HeLa cell manufacturing. So they're not really in the same location. That said, you still have to control the process certainly. I think what all of these reactions including the 2000-liter HeLa cell system has run in disposal bioreactor with proposal system. And so we feel comfortable about the controls of that and have not seen a problem with the question.
Nicole Gabreski -- Piper Jaffray -- Analyst
Okay and then just as a follow-up, you've mentioned that the high cost of GMP plasma production is one reason to use the HeLa system over HEK [Phonetic]. But has there been any thought to bringing plasma to production in-house to reduce costs. And if so, what were your reasons for against this?
Emil D. Kakkis -- Chief Executive Officer and President
We certainly could become a plasma manufacturer. It just, it adds another level of complexity, supply chain and some people have done that and certainly something that could be done for 293, and we currently have made the decision to build our own plant and we could include plasma production. I think the issue with plasma, is just one cost factor, but the reproducibility factor is another and it include end the scale running 2000-liter transaction is not really possible, most people are using smaller reactor sizes and cooling reactors. But with HeLa we can really run a reproducible growth of cells -- 2000 liters and they're probably going to create a much more robust commercial manufacturing process.
The barrier akin was used for vaccine manufacturing. And we said 2000-liter, but you could make a [Indecipherable] if it undergoes 10,000-liter, and no one is doing plasma transaction of 10,000-liter. So we think the HeLa system is what we think of -- it's sort of the next generation, where you're going to create truly commercial AAV manufacturing, with the kind of cost structure and reproducibility required for a truly commercial AAV program, we are still using 393, it can be done in these rare indications and it's certainly can be faster upfront, but long-run, we strongly believe in the HeLa producer cell lines to approach as a better approach to long-term commercial AAV manufacturer.
Nicole Gabreski -- Piper Jaffray -- Analyst
Great. Thanks.
Operator
Your next question comes from the line of Yaron Werber from Cowen. Your line is now open.
Yaron Werber -- Cowen and Company -- Analyst
Great. Thanks for taking my question. So, maybe about two on gene therapy. Maybe just a follow-up for Shalini. So a quick question relating to. So help us to consider the plan in terms of 301, is the -- after this initial three patients, is the thought next to give steroids and then figure out sort of what the next step and you will expand into a few more patients. I'm trying to get a sense, at what point do you also make a decision whether you want to try a higher dose? And I have a follow-up as well.
Emil D. Kakkis -- Chief Executive Officer and President
Well what we're planning to do, we're still continuing the current protocol doing with three. If we see two out of three, that achieve substantial responses that will continue, then do the second group of three at that dose without steroids. The protocol is to add another whole arm of the study and say let's do that same thing, but now add steroids to the arm as the comparator arm. To do it, no matter what we see in the two arms. The idea is if we get a really good response, could we get an even better response with steroids. So that's the argument. We could certainly go higher, it's not an option off the table. However if we get to where we need to be in the range. If you can add something as simple as temporary steroid usage to enhance it further and potentially a couple of fold improvement is possible. We think that's a really simple thing, that's a better answer than simply increasing the dose to get what we want. So right now if you look a lot of gene therapy programs, that won't doing this one linear thing and making tweaks inline, no one is doing comparative experiments and we think this is a good situation, where we should do a comparative experiment and look with a group of patients without steroids how they do and then add the steroids and make a good decision on Phase 3.
So hopefully that gives you an idea. We're going to use the three without steroids that we've done, we'll look at their results and we will add another three assuming a two or three-responders. And then steroid arm will be another arm that will add regardless of how that's proceeding, to tell us whatever effect we're getting can we enhance it further by a simple addition of steroids.
Yaron Werber -- Cowen and Company -- Analyst
Okay, got it. And shifting to 401 depending on obviously what you see in the next dose cohort but the prior dose cohort was probably pretty good. It sounds like you will expand and then we'll figure out what we're going to do with the steroid element. But in terms of a potential registrational path to starting Phase 3 next year, what do you think a Phase 3 trial design may look like based on what you know now, in terms of endpoints?
Emil D. Kakkis -- Chief Executive Officer and President
Well, our general view right now is that for these metabolic disorders, the FDA's preference will be to have control studies. And since they're metabolic we believe it's a metabolic endpoints would make them more tractable. And for example, doing a pure clinical endpoint. So for 401 we've been looking at time of hypoglycemia but we're also working whether hypoglycemia or cornstarch removal and maintenance of glucose stability but it's going to be around the glucose control issue whether it's during the time to have a glycemia or some aspect of glucose control, which we think is tractable and relevant for FDA.
We haven't yet discussed it with the FDA. We think of a program that will likely be, for example, maybe 30 patients -- 20 treated, 10 placebo kind of a study as an idea how where this needs FDA discussion before we complete that plan. But that's the kind of thing we were thinking about in our current planning. And we are planning for both program to be in Phase 3 next year, that is our plan but we just want to make sure that we share -- redo in Phase 3, we've made the best choices.
Yaron Werber -- Cowen and Company -- Analyst
Okay. That's great. And any update on potential KHK timing to filing for a label expansion by age in Europe into the adult segment for XLH?
Emil D. Kakkis -- Chief Executive Officer and President
Well I know that they are planning to put together the filing. Vlad, do you have any update that they've put forth publicly, because I don't know if they've disclosed that publicly.
Wladimir Hogenhuis -- Chief Operating Officer
I don't know if they've disclosed that publicly.
Emil D. Kakkis -- Chief Executive Officer and President
Well, historically we know they've been putting it together, they have all the information required. And so I think it's in their court to make the filing. But if they haven't disclosed it yet, we have to let them disclose what they're doing in Europe.
Yaron Werber -- Cowen and Company -- Analyst
Okay. And then maybe last question is for Shalini. So when we calculate the KHK sales and that they reported this morning was around $70 million and you're reporting $73.5 roughly. So is the delta Latin America which KHK has not reporting and now potentially Canada or is there something else that we're not seeing?
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Yeah, no, it's a good question, in the way they report, in the way we report are very different as hard to reconcile the two. But the couple of differences are that we book sales in Latin America as you noted. And also if you read the footnotes of their disclosure is they do not include any early access or named-patient sales in their total revenue figure.
Yaron Werber -- Cowen and Company -- Analyst
Okay, terrific. Thank you.
Operator
[Operator Instructions] Your next question comes from the line of Adam Walsh from Stifel.
Adam Walsh -- Stifel -- Analyst
Hey guys, thanks for taking my questions. I have two brief ones here. The assay you used to measure the increase in your ureagenesis in the 301 OTC gene therapy trial. I believe, as measured by a label sodium acetate assay. Can you speak to the historical variability observed with that assay and how you're accounting for any potential assay variability in the trial? That's first. And then for the second one on UX007 based on your filing package in most recent FDA interactions, can you comment on your current level of confidence for the NDA acceptance and ultimate approval of the drug? Now that the filing has been made, any color there would be helpful. Thank you.
Emil D. Kakkis -- Chief Executive Officer and President
Very good. So on the assay for ureagenesis question, the assay was developed by a consortium for urea cycle disorder, it's an NIH funded consortium and they've been doing that work for a number of years, and feel it's the best method to assay ureagenesis. Usually patients when repeatedly measure are within 10% of where they were around in that range. And if you look even in our study, we have some patients that are pretty stable within a range. We've had on occasion, people who have not been, but we are doing collecting more data now to help define that variation, but it appears over repeated period of time, reasonably consistent. So we feel as long as this has done in the prescribed way and that is one of the sources for variation, the patient is happy, fasted and cannot sneak food in while they're doing that test for example.
So as long as they do it in the prescribed way, it can't be consistent and feel the variation should be less than 10%. Therefore, the amount of change we're seeing in the patients that we're calling responders as well past what you would observe just through variation, to answer that part. The second question you asked with an 007 our level of confidence. Well, we've had great and detailed discussion of FDA both the pre-NDA and previously an ongoing dialog on assuring that we're providing the information, so we have a high confidence that the filing will be accepted and reviewed. We feel that between the time they accepted the filing for review, let's get to review, we added additional 20 patients worth of data. Another third [Indecipherable] of naive patients treated that had an 80% reduction in the median number of days in the hospital from 10 days to two, consistent with the prior data that we had in our Phase 2 study, as well as in the retrospective study.
So we feel actually they are getting more data now than they actually had when we made the decision. In addition to that we've added expanded access information we've been collecting, which we think is strongly support of. So our confidence is high that it is packages and sufficient size of the 150 patients exposed, some of them for more than 10 years of continuous exposure, combined with the magnitude and the seriousness of the type of data we're talking about. These aren't small changes in hospitalization rates, these are very large changes and very substantive clinically meaningful types of changes. Combined that with the safety profile of a drug that is simply a GI oral drug, there is some GI upset issues but no observed toxicities. At downside I think the benefit of risk is pretty strong and we feel -- we feel confident, we can get through this review and get approved.
As said the FDA had questions they raised, and we will have to work through those questions in the process with them, and they're good questions and we want to make sure we're getting the right answers.
Adam Walsh -- Stifel -- Analyst
Great. Thanks, Emil.
Operator
Your next question comes from the line of Cory Kasimov from J.P. Morgan. Your line is now open.
Unidentified Participant
Hi. This is Nina [Phonetic] on for Cory. Thanks for taking the question. Just want to ask two quick questions. So one kind of a higher level question, just about, you talked about the Medicare and Medicaid exposure in the U.S. And just wanted to hear a little bit about your thoughts on the recent pricing proposals and how that might impact the business going forward in the nice top one? Quick follow-up.
Emil D. Kakkis -- Chief Executive Officer and President
Very good. Well, we don't look at the Medicare -- Medicare exposure is risk. We look at is benefit now that they are proving creating policies and our hearing the stories of our patients and are responding with support for policies to treat patients. So far we think the fact that a bigger percentage is going to just to show you that there is that much interest in support for this drug, because of its profound impact that we've been seeing in terms of rickets and other aspects of the disease. So we're confident that I think the question on pricing and reimbursement questions that are going on in --, similarly a lot of proposals on the table, we have a Government Affairs group and we follow it closely. I think the issues that people ask about is whether reference pricing to Europe would cause us problem. And I would say for that particular issue we have been very thoughtful about how we work together with our Kirin on pricing strategy and we feel that the pricing from Europe, U.S. is actually not differentiated and should not have an impact on us. We think in a significant way unlike maybe some other situation.
So, we feel like we are in good shape from that standpoint. I think fundamentally from all pricing conditions, rare diseases and these kind of very rare disease and very profound effect of drug. I just think it's kind of thing that people are always going to want to get done and I think there is a lot of larger market situations where there is really huge amounts of money and issues at hand, that I think are important, but we believe the rare disease space is special and that there will be whatever happens, people and parents want their kids get treated. So that's going to happen.
Unidentified Participant
Okay, great. And then just one quick follow-up, are there any updates on the filing plants for TIO for Crysvita?
Emil D. Kakkis -- Chief Executive Officer and President
We haven't yet provided TIO guidance, we are working with the FDA on that, our hope and expectation is that we could be able to file, but we want to confirm all the details at this point. But when we get those details confirmed, then we'll update the Street on TIO, but we continue our discussions and we expect that we will be able to file but the details are yet to come.
Unidentified Participant
Okay, great. Thank you.
Operator
Your next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.
Unidentified Participant
Hi, thanks for taking the question. This is Ross on --, I know you said you're planning to file the IND for Wilson's in 2020. Just as we kind of think about what a clinical program and Wilson's disease can look like. Could you just help us understand what a clinical trial would be like here and what endpoints would be of interest?
Emil D. Kakkis -- Chief Executive Officer and President
Yeah. Thank you. So Wilson disease fortunately for us is a disease that has had other therapeutic approved which gives us a lot more knowledge about the clinical regulatory path. And particularly Wilson has the use of pre-serum [Phonetic] copper as a metabolic biochemical marker, that is except, and was -- and is the primary endpoint in the [Indecipherable] copper, the new chelator program, this is currently in trial, and has been used in other indications. We feel, then there is a strong basis for using metabolic copper or free copper levels which are abnormal and which you go down when you use our gene therapy in animals. We think also loading a throughput on copper is important, but we think the freeze in copper is clearly the thing that's going to move people. And that said, I think with the gene therapy we're also have to look at what else we are doing for patients who weren't have to look at both liver injury, liver disease, situations as well as CNS, in the study to help support the benefit of the product in the long-run. And so our study, while it might primarily focus on the freeze [Phonetic] in copper and very supporting their biomarkers.
We would expect to also study the neurologic in liver phenotype which are important part of what we look for and benefit. We haven't said what our plan is, our hope is to design something that is more forward-thinking in terms of becoming adaptive and working including a randomized control group initially. And our hope would be to be able to move faster through dose cohort and adaptively design a program that goes into pivotal, to that, they will require discussion with the FDA an agreement and we do not have that yet. But we think that the signals from the FDA have been that they are looking at ways to provide smoother, more contiguous development programs. And we think this Wilson is a very good choice for that plan because there is clinical history and established endpoints from the past.
Unidentified Participant
Great. Thank you.
Operator
I am showing no further questions at this time, I would now like to turn the conference back to Mr. Danielle Keatley. You may proceed.
Danielle Keatley -- Senior Director of Investor Relations and Corporate Communications
Thank you for joining us today. This concludes our call and a replay will be available soon. If you have any additional questions, please contact us by phone or at [email protected]. Thanks for joining us.
Operator
[Operator Closing Remarks]
Duration: 69 minutes
Call participants:
Danielle Keatley -- Senior Director of Investor Relations and Corporate Communications
Emil D. Kakkis -- Chief Executive Officer and President
Wladimir Hogenhuis -- Chief Operating Officer
Shalini Sharp -- Chief Financial Officer and Executive Vice President
Camille Bedrosian -- Chief Medical Officer and Executive Vice President
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Maury Raycroft -- Jefferies LLC -- Analyst
Gena Wang -- Barclays -- Analyst
Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst
Arlinda Lee -- Canaccord Genuity -- Analyst
Unidentified Participant
Vincent Chen -- Bernstein -- Analyst
Laura Chico -- Wedbush Securities -- Analyst
Yigal Nochomovitz -- Citigroup -- Analyst
Jeffrey Hung -- Morgan Stanley -- Research Analyst
Nicole Gabreski -- Piper Jaffray -- Analyst
Yaron Werber -- Cowen and Company -- Analyst
Adam Walsh -- Stifel -- Analyst
