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Ultragenyx Pharmaceutical Inc (RARE) Q4 2020 Earnings Call Transcript

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Ultragenyx Pharmaceutical Inc (NASDAQ: RARE)
Q4 2020 Earnings Call
Feb 11, 2021, 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 Fourth Quarter and Full Year 2020 Financial Results and Corporate Update Conference Call. [Operator Instructions] I would now like to turn the conference over to your host, Mr. Joshua Higa. Sir, you may begin.

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Joshua Higa -- Director of Investor Relations and Corporate Communications

Good afternoon, and welcome to the Ultragenyx financial results and corporate update conference call for the fourth quarter and full-year 2020. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. I am Joshua Higa, Director of Investor Relations, and joining me on this call today are Emil Kakkis, Chief Executive Officer and President; Camille Bedrosian, Chief Medical Officer; Erik Harris, Chief Commercial Officer; and Mardi Dier, our Chief Financial Officer.

I would like to remind investors that this call will include forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as forward-looking in quarterly report on Form 10-Q that was filed on October 27, 2020, our annual report on Form 10-K that will be filed soon and our subsequent periodic reports filed with the SEC, which will all be available on our website in the Investors section.

These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statement. For further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks related to our business, please see our periodic reports filed with the SEC.

I'll now turn the call over to Emil.

Emil D. Kakkis -- President and Chief Executive Officer

Good afternoon, and thank you everyone for joining us today. 2020 was a transformative year for Ultragenyx as we executed on many of our strategic priorities. We now completed the fourth approval from our portfolio we had at IPO and over the last couple of years, it now refilled our portfolio with substantial opportunities in six clinical-stage programs, four of which are entering pivotal studies. We also have 14 preclinical programs and are advancing our first mRNA program to the clinic this year. The efficient conversion of our pipeline to our next opportunities will allow us to accelerate our value creation and treat more rare disease patients with the first-ever specific treatment. From a commercial perspective, we achieved the upper end of Crysvita revenue guidance despite a global pandemic and received two U.S. approvals and launched treatment for two more diseases with no other approved treatments.

From our clinical programs, we released important data updates from our gene therapy programs in GSD1a and OTC deficiency, as well as the first glimpse of results for the antisense oligonucleotide GTX-102 in Angelman syndrome. Those initial arrangement results suggest promising activity in this relatively large rare disease with no approved therapies, but certainly much more to do to realize the potential. On the gene therapy side, we initiated one of the largest ever gene therapy licensing deals by providing nonexclusive rights to Daiichi Sankyo to utilize our manufacturing platform, including our HeLa producer selling technology. Later in the year we partnered with Solid Biosciences in Duchenne muscular dystrophy to pair their differentiated microdystrophin construct with our AAV8 variance and our producted HeLa PCL system.

Most recently we broke round and began construction on our gene therapy manufacturing facility in Bedford, Massachusetts, that will initially provide 30 manufacturing runs per year at the 2000-liter manufacturing scale. Ultragenyx now has one of the broadest gene therapy franchises, which originated from our acquisition of Dimension Therapeutics in 2017. Our portfolio now includes three in-house pivotal clinical stage programs, one additional clinical program partnered with Bayer with two publicly disclosed in-house pre-clinical programs. Our robust HeLa PCL manufacturing platforms enable us to make AAV vectors at large scale, the highly efficient robust process that will enable the next generation of larger clinical programs.

But that was just the gene therapy side of the business. Our development strategies to choose the right modalities for each disease and we have a variety of other therapeutic modes in our portfolio. For a genetic disease of bone, monoclonal antibodies can be the most effective way for affecting change in their biology. December, we added a new late-stage monoclonal antibody program by our collaboration with Mereo BioPharma. Setrusumab or UX143 has completed a Phase 2b study in adult patients with multiple tides of osteogenesis imperfecta or OI, which is one of the largest rare genetic bone diseases and significantly more common than XLH. Camille will provide more detail on this program later, but I will note that OI and the UX143 program are perfect complement for our bone franchise and the expertise, we have built with Crysvita. The learnings from our Crysvita [Phonetic] redevelopment program will be very helpful in the future development of UX143, and there is significant overlap between the physician to treat OI, XLH and TIO.

Importantly this collaboration provides us to commercialize the product throughout the world with the exception of Europe, where we would see the royalty. While 2020 was a year full of unforeseen challenges, Ultragenyx was able to make substantial progress executing our strategic plan across our pre-clinical, clinical and commercial programs with great success this past year.

I'll hand it over to Erik provide more detail on our commercial performance for the year.

Erik Harris -- Chief Commercial Officer and Executive Vice President

Thank you, Emil and good afternoon everyone. I'm truly proud of how the commercial team executed in 2020 in the face of never before seen challenges. 12 months ago, pre-COVID, we issued guidance for Crysvita revenue in our territories of $125 million to $140 million. Despite the stay-at-home orders, many doctors' offices temporarily closing to non-essential in-person visits and all the uncertainty with global pandemic, we were able to finish the year at approximately $139 million, right at the top end of our guidance range. For 2021, we have issued guidance of $180 million to $190 million for Crysvita revenue in Ultragenyx territories. This represents between 30% and 37% year-over-year growth as we kind of the fourth year of Crysvita's launch. This steady growth is enabled by the many digital strategies to educate physicians and finding XLH patients and getting these patients all Crysvita while ensuring that existing patients, they are on Crysvita during this pandemic.

We believe we will continue to see the mix of XLH patients on Crysvita shift toward a greater portion of adult patients. This will be driven by our increasing efforts on finding adult patients by expanding our reach out to more endocrinologists, nephrologists and other specialties in the communities side. To support these efforts, we will expand both our commercial and medical field teams who will be focused on these harder to find adult XLH patients. In the middle of last year, we launched a TIO indication for Crysvita. The launch is going very well. We have converted the majority of clinical trial patients to reimburse drug and are receiving start forms for TIO patients from the major metabolic bone centers.

Reimbursement for TIO is progressing well and is consistent with XLH reimbursement at the same stage of launch. We will not be providing specific patient numbers for TIO as sales and that indication are included in our overall Crysvita revenue guidance.

Outside of the U.S., we are making steady progress in our discussions with health and reimbursement officials. Demand remained strong across Latin America, as we continue to see more and more patients being granted injunctions required to gain access to named-patient sales. The ordering patterns from the health authorities in this region tend to be inconsistent leading to some revenue lumpiness, which is consistent with other rare disease products in that region. We will keep you updated as we look forward to receiving full reimbursement in other Ultragenyx territories.

Moving now to Dojolvi, which was also launched in the middle of last year for the treatment of Long-Chain Fatty Acid Oxidation Disorders in the United States. At the end of December, we received approximately 190 completed start-forms from approximately 90 unique prescribers of Dojolvi, which speaks to the breadth of interest, we are seeing for this product launch from the physician community. This led to approximately 130 patients on reimbursed commercial therapy, which also includes all 80 patients who participated in our clinical studies. We are also seeing strong support from payers. As of the end of January 2021, over 100 million lives in the U.S. have Dojolvi coverage from over 40 policies, which includes some of the largest national payers. In these first quarters of the Dojolvi launch, we will not be providing revenue guidance and believe the start-forms and prescriber metrics provide a better sense of the strength of the launch.

With that I will turn the call over to Mardi to share the financial results.

Mardi Dier -- Chief Financial Officer and Executive Vice President

Thanks, Erik. Good afternoon everyone and thank you for joining today's call. We issued a press release earlier today that included a financial update, which I will briefly summarize. Company revenue for the year ending December 31, 2020 totaled $271 million. Crysvita revenue in Ultragenyx territories was $138.9 million including $128.6 million from the North American profit share territory and net product sales of $10.4 million in other regions. Total royalty revenue related to the sale of Crysvita in the European territory was $14.5 million. Mepsevii revenue for 2020 was $15.3 million. We expect these revenues may increase modestly over time. Dojolvi revenue for the year was $13 million. This includes approximately 5 months of revenue after the U.S. launch of Dojolvi toward the end of July ended -- and 12 months of named-patient sales in other regions.

2020 total revenue also included -- includes $89.2 million of non-cash revenue related to the tech transfer services provided to Daiichi Sankyo as part of our strategic manufacturing partnership around the HeLa PCL and HEK293 technologies. Our total operating expenses for the year were $601.1 million, which includes research and development expense of $412.1 million and SG&A expenses of $182.9 million. In 2021, we expect our R&D costs to increase as we support three pivotal gene therapy clinical studies, setrusumab Phase 2, 3 clinical study in OI. UX053, our first mRNA Phase 1-2 clinical study and GSD 3 and a number of other IND enabling activities as we get ready to advance the next programs into the clinic.

We expect SG&A to modestly increase in 2021, as we continue to support the expansion and launches of Crysvita, Dojolvi and Mepsevii. For the year ended December 31, 2020, net loss was $186.6 million or $3.07 per share. This compares to a net loss for the same period in 2019 of $402.7 million or $7.12 per share. Net loss for the year ended December 31, 2020 includes $170.4 million increase in the fair value of investments in equity securities. Net cash used in operations for the year was $132.2 million, compared to $345.4 million for the same period in 2019. We ended 2020 with $1.2 billion in cash, cash equivalents, and marketable securities. This puts us in an excellent position to be able to support the execution of and achieve key milestones in our late-stage clinical pipeline and commercial expansion.

Now I would like Camille touch on some of our clinical programs.

Camille L. Bedrosian -- Executive Vice President, Chief Medical Officer

Thanks, Mardi, and good afternoon, everyone. On January 8th, we issued a comprehensive press release, the detailed the latest data, regulatory progress, and Phase 3 plans for our gene therapy programs. Therefore, today, I will briefly summarize our current status and next steps for our three pivotal stage gene therapy program. DTX401 for glycogen storage disease Type 1A has completed the scientific advice process with the European Medicines Agency, or EMA, as well as held an end of Phase 2 meeting with the FDA. Out of these meetings, we have aligned on the Phase 3 study design and endpoints. We currently are on track to initiate this pivotal study in the first half of 2021.

Shifting now to DTX301, for ornithine transcarbamylase, or OTC, deficiency. We have received feedback from our initial scientific advice discussions with the EMA and will have an end of Phase 2 meeting with the FDA, barring any unforeseen delays by the end of this quarter. Based on the initial discussions, we feel confident about where we will end up with regards to the design and endpoints for this Phase 3 study. We currently are on track to initiate this study in the second half of 2021.

Moving now to UX701 for Wilson disease, our third third pivotal gene therapy program to enter the clinic in 2021. Earlier this year, we announced that the seamless single protocol Phase 1, 2, 3 IND application has cleared FDA review. The program also recently received Fast Track designation, which will enable additional dialog and feedback from the FDA. This study currently is on track to initiate in the first half of 2021.

Now I will touch on GTX-102, an antisense oligonucleotide which is being developed with our partner, GeneTx, for the treatment of Angelman syndrome. Angelman syndrome is a devastating neurogenetic disorder with a broad spectrum of disease manifestations, including speech and cognitive impairment, ataxia or balance issues, sleep dysfunction, and seizures. GTX-102 is the first antisense oligonucleotide program for Angelman to reach the clinic.

Late last year, we announced positive interim data from the ongoing Phase 1, 2 study of GTX-102. All five patients who were treated demonstrated improvements in at least three disease domains and scores of much improved or very much improved, and two disease domains as measured by the Clinical Global Impression of Improvement Scale for Angelman syndrome. These improvements were also supported by other increases and measures, including Observer Reported Communication Ability, or ORCA, and daily for communication scale, as well as by preliminary EEG reading. All five patients also had a Grade 1 or 2 serious adverse event of lower extremity weakness associated with local inflammation in the region of administration in the lower back at the higher doses of GTX-102.

Dosing was paused after the first SAE onset was observed and the study is currently on clinical hold. The SAE has fully resolved in all five patients and clinical improvements have been sustained beyond the resolution of the SAE. GeneTx, our partner, has submitted to the FDA, a substantial information amendment including follow up safety information for the five patients dosed and non-clinical data in non-human primates. We have proposed an amended dosing and administration plan to the FDA. These changes are expected to reduce the local contact time and concentration of the ASO.

Furthermore, the new dosing plan is within the observed range of the clinical activity, but well below doses associated with SAE's. GeneTx received some questions from the FDA and responses were provided. We currently expect the study to resume enrollment and dosing in the first half of 2021 following resolution of FDA requests and approval to proceed. Once we started, we expect additional interim data from this study that are expected in the second half of 2021. We are also in the process of expanding the study to other countries, including Canada, where clinical trial application was previously filed, a protocol and information amendment similar to that proposed to FDA will be submitted.

Our first pivotal program to enter the clinic in 2021 will be the UX143, or setrusumab, a monoclonal antibody for the treatment of osteogenesis imperfecta or OI through our partnership with Mereo. OI is an extremely serious bone disease where defect in collagen result in significant bone fragility leading to stiffness, pain, factors, and deformities. Oftentimes OI is believed to be a result of weak collagen, but based on our sponsor preclinical work and others research, we now understand that the major cause of bone weakness in OI is due to excess bone resorption triggered by the abnormal collagen and the inadequate production of new bone leading to low bone mass. These data show that if you could simply increase bone formation and reduce the excessive bone resorption, you kind of increase bone density and improve bone strength, even with the abnormal collagen and achieve improved fracture prevention.

We believe this is the insight that could change the future for patients with OI. Mereo has released Phase 2 data in 90 adult patients with OI, randomized among three different dose levels. The patients were dosed monthly for 12 months. Study results indicated substantial improvements in bone mineral density in uptight OI Type 1, 3, and 4, the three types included in this study. This response was dose-dependent and observed across different anatomical sites. The study also showed an ability to create a significant amount of bone, which we believe is a very important factor in improving bone strength. The safety profile for setrusumab is favorable for patients with OI.

Pending discussions with regulatory agencies, we are planning to enroll the Phase 2, 3 study in pediatric patients. The first will identify the optimal dose based on increases in the serum bone formation markers P1NP and enroll into a randomized control period, looking at fracture rate reduction and bone mineral density over an estimated 15 to 24 months. While a separate pivotal study also is being planned for adults with OI, we believe the pediatric population will give us the fastest avenue for approval for the product. We currently expect to initiate the pediatric Phase 2, 3 in the second half of 2021.

The last program, I will briefly summarize is UX053 for glycogen storage disease Type 3, or GSD3. GSD3 is an inborn era of metabolism caused by mutations in the agLG, which is responsible for the production of the glycogen debrancher enzyme. A deficiency of the debrancher enzyme impairs the breakdown of glycogen in the liver and leads to a toxic residual carbohydrate. To our license from Arcturus, we have developed an mRNA with N -- with a nanoparticle product that is intended to restore the debrancher enzyme function thereby clearing the accumulated toxic residual carbohydrate and normalizing glycogen metabolism in the liver. We are currently on track for an IND in the first half of 2021 and to initiate a Phase 1, 2 study in the second half of the year.

I will now turn the call back to Emil, to wrap up.

Emil D. Kakkis -- President and Chief Executive Officer

Thanks, Camille, Mardi, and Erik. 2021 is going to be a full year of lots of important progress across our commercial and clinical programs. The active work and BD has refilled the pipeline with multiple late-stage catalysts with one of the best rare disease portfolios in the business. In the commercial portfolio, we're looking forward to continue expanding Crysvita in the adult market through greater efforts to find patients and outline clinics and through pedigree analysis. We are also continuing to expand Crysvita use outside the US, Latin America, Canada, and Turkey. We drove this off to a strong start and I know the team will continue to execute launch for patients with LC-FAOD. We are in great and urgent need for a new treatment option. Our commercial Mepsevii [Phonetic] have adapted well -- very well, the launching three products in four disease in the COVID environment. Within our gene therapy business, we've broken ground on the manufacturing facility embedded for Massachusetts and three programs going at least late stage clinical trials. We continue to advance our early stage work in new muscular disease a CDKL5 deficiency and Duchenne muscular dystrophy. We are also continuing to improve on the HeLa manufacturing technology with the new 3.0 system that will have even higher productivity and reduce COGS making gene therapy a viable modality for these larger higher dose indications on a global basis.

Our nucleic acid therapeutics pipeline will also advance. We're making progress in reviewing the ASO Phase 1/2 study in Angelman. We plan to initiate clinical development for the mRNA UX053 and glycogen storage disease type III or debrancher deficiency. With our first mRNA probing to come out of our license, Arcturus and that license also provides rights for up to 12 mRNA and other nucleic acid therapy targets.

The GSD3 program is also a great complement to our efforts in GSD1a and builds on our broader portfolio therapies aimed at inborne areas of metabolism that have not been treated by more traditional means. The addition of setrusumab gives us a de-risk wastage from the leverage expertise in creating clinical pathway for rare genetic bone diseases. As you can see we're in a great moment in our evolution to the company with multiple late-stage assets across therapeutic areas, modalities all enabled by continued strong financial performance from our proved programs, strategic investing in fiscal diligence. Now let's move on to your questions. Operator, please provide instructions for the Q&A portion of the call.

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Emil D. Kakkis -- President and Chief Executive Officer

Hello, Maury. Hey there, Maury. Well, it's a very good question. We are doing great and thank you for asking. Maury, may be you are on mute. Operator can we go onto the next caller until Maury gets his vacation fixed?

Operator

Yes, sir. Your next question comes from the line of Yaron Werber from Cowen. Your line is open.

Yaron Werber -- Cowen -- Analyst

Hey, good afternoon and thanks for taking my question. So, Emil, I got maybe the first question, the pipeline is now -- looks really good. I mean you've essentially two drugs going into pivotal, another one potentially into a Phase 2/3, I mean it's fairly full. Do you have more room for BD, are you still looking or you are sort of good for the next year? And then, Mardi. I don't know if you can give us any sense how do we model Daichii related revenues? Do you have visibility that you could share with us? Thank you.

Emil D. Kakkis -- President and Chief Executive Officer

Great, Yaron. I think if you look at our portfolio, we tend of target having 5 to 7 clinical stage programs and right now we would have six with what we're dealing. So we're on a relatively full state in terms of development stage programs. We are still continuing to be because you always continue to look if there were something amazing, we wouldn't want to walk past it, we would look for that opportunity, but we are potentially have ability to leverage our commercial organization with later stage opportunity, but I do believe them from earlier development stage opportunities, we're very full. We've been on and off and we've got a lot of work to do, and I'm excited about the portfolio. I don't think we can imagine being in a better place than what we've been able to put together over the last couple of years. So Mardi, maybe you can answer the other question.

Mardi Dier -- Chief Financial Officer and Executive Vice President

Yeah, real simply Yaron with Daiichi, of course, the deal that we completed back in March was for a $200 million upfront. From an accounting purpose, we have this non-cash revenue recognition that we believe is associated with the tech transfer of the deal. So there is about $60 million plus left on that recognition of revenue and that should be complete in 2021, so that should be a pretty specific way to model it in 2021.

Yaron Werber -- Cowen -- Analyst

Great, thank you.

Mardi Dier -- Chief Financial Officer and Executive Vice President

Yeah.

Operator

Your next question comes from the line of Gena Wang from Barclays. Your line is open.

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. I have two questions, one is regarding the Angelman Syndrome. It seems that FDA already gave you feedback and Emil, just wondering if you can give a little bit more color regarding the amendment to the protocol. If there any additional change versus your original submission regarding the protocol amendment? And my second question is regarding the dosing change you use ddPCR for the GSD-Y pivotal study and change the dose from 6e12 to 1e13 and just wondering do you need to do similar change for the OTC program? And will you use ddPCR across all the future program, so that the dosing will be more accurate going forward?

Emil D. Kakkis -- President and Chief Executive Officer

Sure. Great. So on the Angelman, we gave in this very large substantial amendment. They provided then a response to some specific questions. Additional information inquiry that they were interested in. They -- those questions did not change the plan we had proposed. We listened to what they put together and provided now -- an amendment to the protocol and IRB, etc. and all the things required in order to proceed ahead. So we'll wait and see their response to that. But the questions didn't really change our plan. They were basically in line. I think we -- our plan is pretty well thought out. I don't think that there is -- I think there is not much we can do to change, but we'll wait and see for their feedback and there may be subtle ways to manage it and they will want to assure safety, just like we do and we're happy to work with them to get that done, but we feel comfortable, we're going to get back into the treating these patients and the patients have been inquiring they really want to get back to treatment. So we want to get back to it, I think we're in good shape for that and we'll see what they say.

On the GSD1 story, we're not really changing the dose, what we're doing is changing how we're measuring the dose. So what -- it's really important that total doses that we're giving the same as it was before. It's just what we're calling it has changed and what's happened is that the original qPCR methods have some limitations and variability in them. They're not as good and we've been working on the digital drop method, which is high more reproducible, more validatable and therefore a more accurate representation. What it turned out for GSD1a is that, we were really -- the amount of vector we're giving which we considered 6e12 before was actually closer to e13 when you use a more accurate digital drop method and it just relates to the techniques and the basis of certain techniques.

For the OTC program, there is also a difference and we are using the digital drop, but would it be clear to the everyone is that the dose is the same as it was, it's just what we're labeling the dose as based on a more accurate method and this is one of the things, even FDA has been on and we all want is to continue to improve the quality of the methods, to give us accurate representation of how many of these particles are alive and well in its vector product that we can use for gene therapy.

So practically speaking, it doesn't change anything, but from a standpoint of the quality of the process, it helps give FDA and ourselves confidence of what we're administering in every lot.

Gena Wang -- Barclays -- Analyst

Great, thank you.

Operator

Your next question comes from the line of Cory Kasimov from JP Morgan. Your line is open.

Cory Kasimov -- JP Morgan -- Analyst

Hey, good afternoon guys. Thanks for taking the questions. First one on Angelman, assuming you do in fact get that study up and running in the first half of the year as you're expecting, how quickly do you think you'll know whether the amended dosing and administration plan is working and avoid any assays you saw originally? And then I have one follow-up on the Wilson's.

Emil D. Kakkis -- President and Chief Executive Officer

Well, the way the protocol is proposed, we will redose the existing patients -- five patients and will also enroll another 12 patients in the staged manner and look at basically four doses and then we'll go into a maintenance every three months. So by the time we get to four months of dosing with these patients in the -- both the five and the additional 12 that will give us a sense of are we getting the efficacy we thought after accumulating the effect over multiple doses at a lower level and are we seeing safety. So, we'd expect to get to that story later in the year because it takes about four months for each patient enrolled to get through the dosing. So we can get through four doses and show the same substantial efficacy we saw before and not have the safety event that helps improve it. Once they go on to maintenance where they are going every three month dosing. I think we feel more comfortable that the safety will be better. The problem we had was only during the monthly phase. So if we can get through the monthly phase, go onto maintenance dosing and we're good through the monthly phase, and get the efficacy, we're hoping for them, I think we'll know and that should happen later this year.

Cory Kasimov -- JP Morgan -- Analyst

Okay, that's very helpful. And then for your seamless Phase 1, 2, 3 for Wilson's, what's the process in terms of making go-no-go decisions here to move to the next stage in this particular type of design? is it -- should we think of it as a truncated study across all three typical phases or is there something else that goes into it?

Emil D. Kakkis -- President and Chief Executive Officer

Well, the two stages. In stage one, we're going to dose of placebo and drug in three cohorts, a first dose cohort 5e12, e13, 2e13. All right. So it's going to be a sequence of patients through three cohorts. During this period, there will be an interim assessment -- a blinded interim assessment to show whether that -- what the dose is looking like and what's happening, and we'll make a decision on dose after those three cohorts. At that point we would know in a blinded fashion in group that we are seeing an efficacy when safety is as appropriate and we'll pick the dose to move forward. So we'd expect somewhere in there to have some data that we would put out that would not -- but we want to make sure not to harm the conduct of the study, but we'll put out some information about where we stand and that we have crossed from dosing stage into the pivotal stage. Is that helpful?

Cory Kasimov -- JP Morgan -- Analyst

Yes, definitely. Thanks, Emil. I appreciate it.

Operator

Your next question comes from the line of Joon Lee from Truist Securities. You may ask your question.

Joon Lee -- Truist Securities -- Analyst

Hi. Thanks for taking my questions. So, Emil, can you affirm that the FDA was generally in agreement that Trendelenburg and lower dosing will be sufficient to avoid the SAEs, or do they want something entirely different? And then secondly, what if any rethrough is there from the failure of OV101 and Angelman is placebo effect possibly an issue when using CGI-I-AS, just curious if there is anything that could be learned from that study to apply to your story? Thank you.

Emil D. Kakkis -- President and Chief Executive Officer

Sure. Well, the FDA did not question Trendelenburg and plus the procedures because actually they had been used widely and I think we provided the justification for that. It has been done by the way in chemotherapy for years, years, now if we've made this up, it's been well established to reduce local toxicity in chemotherapy drug. So it's not like we're something never been done before. So it wasn't really question about that. It was more about what the event is and what's going on, kind of thing. They just want confidence around that we can make the right interpretation of what's happening and our interpretation of it being a local inflammatory event and those required, those just more detailed information about the MRIs and other things so they can kind of understand what we understand. So there was no question about the strategy on lower dosing capping and the other changes at this point. So we feel pretty good about where we're at. I do think we're making the right choices and I think there's good base for our changes to be beneficial.

Now with regard to OV101, I don't think it has too much read-through it. If it was of course an approved product during our Phase 3, it would probably create more complexity for how we're managing patients on it or not on it. With regard to CGI and its value, I appreciate the fact that our five patients were open-label. The magnitude effect that we are seeing is not 0.7 points, meanwhile the average for the five patients was 2.4. So, the degree of efficacy changes far larger than you might see from placebo if that was placebo effect. So in addition to that, there were multiple other evaluations in the trial that supported the communication changes and the other changes observed, including sleep and other things including mobility. So it wasn't just CGI that was actually a whole host of secondary valuations also supporting the change.

So that's why we know this is real and we know it's profound and we were where we think it's something could be quite important for these patients. We know by the way that with the time is passing, of course the patients have the effect lasted maybe four, five months in many of these symptoms, but as time has passed, of course patients have lost some ground and are anxious to get started again. So in our case, I'm 100% confident, this is not placebo effect, we have too much data to support it and of course the magnitude effects just beyond what you would assume to be part of a placebo effect.

Joon Lee -- Truist Securities -- Analyst

And just quickly, following up on the Angelman's. You have not created a target for yourself. There are companies pursuing the exact same approach stop to start. What kind of note do you have around your product that could protect the franchise front well, better?

Emil D. Kakkis -- President and Chief Executive Officer

Well, I think you've got a target to make the first thing you got to run fast. So they're hard to hit. But that's sort of position, but truthful to I think our ability to execute its going to be real important. The truth is, if you want to -- as a company, we will work on some larger rare disease areas. But when we do, it's not to be all alone like some other ones, like OTC, GSD1, GSD3. It's more comfortable, we really pretty much the only clinical play. It will be there. But here's the thing about the whole program. The reason we picked this Angelman program, the work we have done, is that we have the data that we were looking at that they produce in vitro and others, all the work has gone day-to-day, which said what they're doing in the region they're targeting is far more prudent and able to knock down all the antisense transcripts than what other people are doing, is we felt there was a distinct intellectual property scientific insight improvement.

The other method is trying to do what we're doing is actually very hard. I do think the ASO method will be better and the gene therapy will be hard to replicate, because you cannot deliver every neuron evenly and you can't have variations of expression of this thing, they are too high. So it's going to be a lot trickier to deal with this on a gene therapy basis then an ASO basis. Because with the ASO, we enable the gene to be expressed, but we don't force it to be expressed. That allows an endogenous regulatory mechanism to even out the amount of this UBE3A protein. So maybe a little bit scientific detail, what I'm saying to you there is a very strong basis for why this, as it can allow you to get more neurons active and allow them to be regulated properly and I think that's why we believe the ASO was the best method among those and among those ASO methods, we have the best-targeted region and that's our confidence in what we're doing. Same time we're going to run fast.

Joon Lee -- Truist Securities -- Analyst

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

Yigal Nochomovitz -- Citi -- Analyst

Hi, Erik. Hi, Emil, and team. Thank you for taking the questions. So, could you provide a bit of perspective on Ultragenyx strategy to differentiate setrusumab profile from romosozumab, given as you know, both antibodies target sclerostin and in light of the fact that Amgen is also pursuing osteogenesis imperfecta with romo in a Phase 1 that was recently posted on clinical trials? And then secondarily, if you could comment on the advantages of targeting sclerostin as opposed to rancho [Phonetic] or TGF-beta for osteogenesis imperfecta given as you know the Amgen is pursuing OI Phase 3 and OI with Prolia and Sanofi is pursuing with OI with fresolimumab in Phase 1? Thanks.

Emil D. Kakkis -- President and Chief Executive Officer

Good, thank you. It sounds like another variation of target on our back questions, but -- so look, we are very familiar with romo and in fact, Michael Minsky that worked through us, worked for Amgen for 10 years on romo and has a lot of knowledge. It's a good anti-sclerostin antibodies, main commercial potential for Amgen has been around osteoporosis. As part of their development program, there are required to do a pediatric investigational plan for Europe, which requires them to run the study. So if they are running a study, what they will do with that in the long run, it's unclear, but the idea that the tip is just they have to try to test their product in that population, but they're not focused on that population. We are going to look at the dosing and dose regimen uniquely to apply to OI, and we think the dosing may need to be higher and that's in pediatrics, And they're doing therapy for one year, whereas I think we will need to do more chronic or have at least induction in the main -- mean phase, which is not part of their program. So our folks in OI will allow us to depth dosing and regimen to optimize for the OI indication. That said, could people use romo off-label and will we have to deal with that commercially, and I say yes, we will. We still have to deal with it, but OI has a lot of patients and a lot of different types that can be benefited and we think somewhere in there with the dosing and other issues that there is a very important product that we could achieve regardless of what the pricing issues play out.

The second point you asked about is that the other competing molecules. I think sclerostin has some unique features that are particularly good. If you look at OI, the patients have too much resorption, but they also have inadequate bone anabolism [Phonetic]. So you definitely want a strong anabolic agent and we think sclerostin appears to be a very strong anabolic agent and in the animal models that why it's very potent and inducing good bone formation that results in strong bones that persist fracture. So we think that the focus on anabolism with some effect on resorption, I think is probably valuable, especially in the context with bisphosphonate. Certainly TGF-beta is Sanofi is working on is another strategy, its another hormone involved in bone regulation. I don't have a lot to say right now. It could be a factor we'll have to keep our eye on what they're doing, rank Logan [Phonetic] or bases the denosumab is what I assume you're talking about. It's another approach, but it's a little different, it's related more to the absorption. I just think -- we think based on what we're seeing as sclerostin is best and I will also say that sclerostin maybe the first step and maybe there were need ultimately as a second generation version to add another molecule like a combination to optimize but given the size of OI and our particular expertise in running bone development, I have confidence we can push forward a good product that will make a real big difference for OI patients.

Yigal Nochomovitz -- Citi -- Analyst

Thank you. Super helpful. Thank you. Emil.

Operator

Your next question comes from the line of Salveen Richter from Goldman Sachs. Your line is open.

Salveen Richter -- Goldman Sachs -- Analyst

Hello.

Emil D. Kakkis -- President and Chief Executive Officer

Is that Salveen?

Operator

The question has been withdrawn sir. Your next question comes from the line of Liisa Bayko from Evercore ISI. Your line is open.

Liisa Bayko -- Evercore ISI -- Analyst

Hi there, thanks for taking my question. For DTX401 for GSD1a, are you going to be enrolling patients in Phase 3 from all the different kind of mutation types and should we expect similar efficacy across those? Thanks.

Emil D. Kakkis -- President and Chief Executive Officer

So we are not restricting to a particular mutation. But remember in GSD1a about 80% of the patients are null. So it's probably is homogeneous, a phenotype null expression as you can get. And so we feel pretty comfortable that even if there is some minor -- let's say lesser mutation, patients with less effect, less deficiency that we would expect the effect to be as good or better because if we -- most of patient we have been treating being all null. So if we can treat the nulls effectively, then treating the nuance one should be easier, not harder, right. So we feel pretty confident we can treat -- we can treat all based on how many nulls we've already treated.

Liisa Bayko -- Evercore ISI -- Analyst

Okay, thanks.

Operator

Your next question comes from the line of Jeffrey Hung from Morgan Stanley. You may ask your question.

Jeffrey Hung -- Morgan Stanley -- Analyst

Thanks for taking the questions. For UX701, you went through the plans for the single protocol Phase 1/2/3. So going forward, do you see this as a standard way you'll be conducting studies for other gene therapies or was there something specific to this program that allowed sort of single protocol study design?

Emil D. Kakkis -- President and Chief Executive Officer

There are some factors that make single protocol designs possible, and one of the key ones, Jeff is endpoints like primary endpoint and the Wilson case because there's always approved products, we know and the FDA has already agreed that urinary copper excretion can't -- 24-hour urinary copper excretion can be the primary endpoint. With the primary endpoint defined, then you can design entire program straight through. If you don't have a primary endpoint defined, it's a little in hard to try to find the Phase 1/2/3 without having analyzed and configured the right inclusion criteria for the next stage, if that makes sense. So, it really has to do with what were your level of confidence in the endpoints. Now for Duchenne where there is knowledge of the endpoints, and for example, that's one more Phase 1/2/3 maybe possible because of the endpoints have been developed, for CDKL5 is the neurologic disorder, is a little bit different. We're creating new endpoints, that's something where may be a little harder to do a straight through program. In any case, you can design in any way like, separate or together the key advantage of making it one continuous one is that you don't have to go through our regulatory query step in the middle. Right. That's the thing...

Jeffrey Hung -- Morgan Stanley -- Analyst

All right.

Emil D. Kakkis -- President and Chief Executive Officer

That preparing the data submitting, getting the meeting, you burn out eight months, sometimes almost a year of time in there and that's the savings. So wherever we can get confidence from the agency upfront on endpoints and design, then we can try to take that rapid path.

Jeffrey Hung -- Morgan Stanley -- Analyst

Great. And then for Crysvita, you talked about the focus on finding adult patients. What's the current proportion of treated patients that are pediatric. I think in the past, you mentioned, its about 60%. Just curious if that's changed much over time? Thanks.

Emil D. Kakkis -- President and Chief Executive Officer

Yeah. From the new patients I don't know, Erik, you want to add anything to that but basically it's been shifting more toward adult. The terms of the fraction of current prescriptions.

Erik Harris -- Chief Commercial Officer and Executive Vice President

In the last number reported out on this, there is the mix of about 35 to 45, its 5% pediatrics versus 40% adults. We've continued to see the overall share toward -- more heavily toward adult patients and in the last couple of quarters, we've been finding more adult patients than pediatric patients. So we expect that to continue to ship more heavily.

Jeffrey Hung -- Morgan Stanley -- Analyst

Great, thank you.

Operator

Your next question comes from the line of Laura Chico from Wedbush Securities. You may ask your question.

Laura Chico -- Wedbush Securities -- Analyst

Thank you very much and good afternoon. So, just following up on the Crysvita co-promote. So I know it's probably looking a bit ahead, but the co-promotion, is that a change in 2023 and you just mentioned kind of the mix between the ped's and the adult patients. I'm just curious as we're kind of entering the second part of this agreement, is the focus on shifting toward adults. The theme to be thinking about as one of the key drivers to maximize the remaining trajectory or are there other, I guess just the strategic initiatives, we should be thinking about? And then just one quick follow-up with regards to A10 [Phonetic] in DMD. I guess, following a competitor update from a gene therapy study, I'm wondering if you could maybe opine a little bit on how you're thinking about alternative biomarkers in the DMD space? Thank you.

Emil D. Kakkis -- President and Chief Executive Officer

Thank you, Laura. So, with regard to Crysvita, we still have room to penetrate both the ped's and the adult market. We have, we're not finished in that process. So, but we have not do about 30% of the peds. So we continue to work on growing the ped's market as well as the adult. It's just that the adult market -- the unmet need, there is probably a larger number of patients right now, right. And there are a little more of lost a little harder to find. So we are making a big effort. I don't know that it has a great deal to do with the transition is just mainly about optimizing the growth of the product ahead of it. So it really is more about where we see the most opportunity. I don't know if. Erik has anything else to add to that.

Erik Harris -- Chief Commercial Officer and Executive Vice President

The one thing I would add to that is there. It certainly is one of our top priorities in finding the adult patients and we've shifted resources to do just that from both digital and virtual but as well as I stated, there are plans to expand both the commercial and medical VLTs to be able to target more physicians in the community setting where most of the adult patients are, so to take advantage of that opportunity.

Emil D. Kakkis -- President and Chief Executive Officer

Yeah. And I think one of the thing we're doing is because the -- each pediatric patient on drug likely has three or four adults that are related to them on average. Using the pedigree enough to help find relatives across countries is important. I do think it's happening in adults is that we're getting a lot more feedback of adults on treatment and how they're doing and there's a lot more recognition of the adults. There are many adults that need to be treated and I think that's going to help, but if you look at the total number of patients that we can treat, the adult population is I think is still an area, where there is whole lot -- lot more patients for us to transition. So it's all about optimizing the growth of the product, but adults and peds both matter. And we're working with our partner KHK and planning transition, but remember after the transition of course, we continue with the same essential revenue if you look at the revenue post. It's just. We're not doing the commercial as much, but we will be doing promotion of medical genetics after the transition. So we will have a role and promotion for the product in at least one segment of doctors.

So let's talk about the other the biomarker story. So the question, it sounds like you were asking about is, were there any outcome data from through after others which suggests that we should, how do we look at the biomarkers for proving efficacy. I think that the challenge here is that measuring this trough and then doing it accurately and knowing how it means is tricky and I think there is a lot of good methods and I do think we're going to want to look carefully at the methods because I do think they will have an impact on the impression of what you're achieving, I do think though that there is another factor which is how do markers translate really in the clinical benefit, which I think is partly at the question and we are familiar with muscular disease [Phonetic] will help us. The truth is that even if you deliver the compound engaging it into the muscle and integrating it and having an effect on clinical function takes time and in addition with generally in muscle once you've lost function, I have just not seen treatments that bring back function, is almost always about maintaining and not losing. And I think that may be a mindset, we have to think about and that's we're treating early before they lost function is probably going to be important. So we're going to look at the quality of the biomarkers and the sure we're doing things that we think are validatable, but again [Technical Issues].

Camille L. Bedrosian -- Executive Vice President, Chief Medical Officer

Emil, we are having a little bit of audio problem coming from your phone.

Emil D. Kakkis -- President and Chief Executive Officer

Can you hear me all right?

Laura Chico -- Wedbush Securities -- Analyst

Yes.

Emil D. Kakkis -- President and Chief Executive Officer

Okay. I think there may be a problem. My phone may be getting hot from the sun. The company is hot too but anyways.

Laura Chico -- Wedbush Securities -- Analyst

Thank you, Emil.

Operator

[Operator Instructions] Your last question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Maury Raycroft -- Jefferies, LLC. -- Analyst

Hi, everyone. Congrats on the progress and thanks for taking my questions. So I just wanted to check in on Dojolvi. It seems like it's off to a really good start and I'm guessing you're not going to say too much more on traction with newborn patients and naive use. But I'm wondering if you can provide any specifics around progress in screening and getting uptake in these patients?

Emil D. Kakkis -- President and Chief Executive Officer

Yeah [Phonetic]. We haven't -- we don't have any more to report on newborns, ours newborns have been prescribed and we also had some emergency cases still happening that we've had to respond to quickly without the reimbursement process being a whole separate story. So we've been doing some of that already and that continues. I don't really have any more specific about an uptick in the newborns. I think we need to continue to make sure our policies allow patients the numerous be treated. But what I would say to you the patient and wants patient to be treated, we will treat them with a reimbursement come through or not, we will treat the babies and work with the reimbursement process whenever it can be worked. But remember, in this situation, you know, time for -- we time our babies especially if there are symptoms, they got be taken care of, you don't have time for the process and so we're very comfortable with providing free drug assets immediately to patients and then handling the reimbursement process over time. I don't know, Erik, if there is anything else you could provide on the issue of some newborns and naive patients[Phonetic].

Erik Harris -- Chief Commercial Officer and Executive Vice President

I would say that our own cohort has been very responsive with those requests form newborns where we've been able to get product to these newborns is certainly under 24 hours and as early as 6 hours in some emergency cases. So we are set up to address this need for such a fatal disease, life-threatening disease for these newborns.

Emil D. Kakkis -- President and Chief Executive Officer

Yeah, I hope that will help.

Maury Raycroft -- Jefferies, LLC. -- Analyst

Yeah. That's helpful. And last question is just on UX053. Just wondering if you can provide any more perspective on what the study would look like, the types of patients you plan on enrolling and could we potentially see data from now one by the end of 2021?

Emil D. Kakkis -- President and Chief Executive Officer

Yeah, we would expect that we may have some data end of the year, maybe Camille can you provided it early. Just a brief negate on the study. I'm sure it will come up and clinical trials that in ordinate [Phonetic] detail. Go ahead Camille.

Camille L. Bedrosian -- Executive Vice President, Chief Medical Officer

It will. Thank you for the question. Thank you, Emil. Yes, the study is first and foremost the safety study, first out also looking at identifying the dose, dose finding followed by dose-ranging and we'll have a randomized cohorts of patients, placebo, and the drug. And in addition, there'll be multiple doses in the second round of cohorts for the patients. So the patients with GSD3 regardless of mutation and we will start initially with adults, followed by pediatric patients.

Maury Raycroft -- Jefferies, LLC. -- Analyst

Got it. Very good. Thank you for taking my questions.

Camille L. Bedrosian -- Executive Vice President, Chief Medical Officer

Sure. Thank you.

Operator

I am showing no further questions at this time. I would now like to turn the conference back to Mr. Joshua Higa.

Joshua Higa -- Director of Investor Relations and Corporate Communications

Thank you. This concludes today's call. If there are additional questions, please contact us by phone or at IR at ultragenyx.com. Thank you.

Operator

[Operator Closing Remarks]

Duration: 59 minutes

Call participants:

Joshua Higa -- Director of Investor Relations and Corporate Communications

Emil D. Kakkis -- President and Chief Executive Officer

Erik Harris -- Chief Commercial Officer and Executive Vice President

Mardi Dier -- Chief Financial Officer and Executive Vice President

Camille L. Bedrosian -- Executive Vice President, Chief Medical Officer

Yaron Werber -- Cowen -- Analyst

Gena Wang -- Barclays -- Analyst

Cory Kasimov -- JP Morgan -- Analyst

Joon Lee -- Truist Securities -- Analyst

Yigal Nochomovitz -- Citi -- Analyst

Salveen Richter -- Goldman Sachs -- Analyst

Liisa Bayko -- Evercore ISI -- Analyst

Jeffrey Hung -- Morgan Stanley -- Analyst

Laura Chico -- Wedbush Securities -- Analyst

Maury Raycroft -- Jefferies, LLC. -- Analyst

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