Q1 2020 Earnings Call

Well below.

Operator: Operator. Please stand in line for the next available operator. Please stand in line for the next available operator. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience. Please stand in line for the next available operator. Thank you for your patience.

[music].

Thank you for your patience.

[music].

Leasable.

[music].

Sellable operator.

[music].

Operator: Please stand in line for the next available operator. [inaudible] Thank you for calling out a conference. Uh, yes, it is 9-4-5. Hi, yes, can you hear me? I can barely hear you.

Well.

[music].

Unknown Attendee: There's something going on in the background that's creating feedback. Oh, sorry. I don't really have another way to switch the audio.

Mobile.

[music].

Unknown Attendee: I have a pin I can give you if you can hear it. It's 9455159. Okay, may I have your first and last name? Catherine Harrison. Is Catherine with a K or a C? With a C. May I have your company name? Aira, A-I-E-R-A.

Hello.

[music].

<unk>.

[music].

Operator: Thank you, please sign in. Ladies and gentlemen, thank you for standing by, and welcome to the Ultragenyx First Quarter 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

Hello.

[music].

Operator: Please be advised that today's conference may be recorded. If you require any further assistance, please press star zero. I would now like to hand the call over to your speaker today, Ms. Danielle Keeley. Please go ahead.

Well.

[music].

Danielle Keatley: Good afternoon, and welcome to the Ultragenyx Pharmaceutical Financial Results and Corporate Update conference call for the first quarter of 2020. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. My name is Danielle Keatley, Senior Director of Investor Relations.

Well.

[music].

Well.

[music].

Danielle Keatley: Joining me on this call are Emil Kakkis, Chief Executive Officer and President, Shalini Sharpe, Chief Financial Officer, Camille Bedrosian, Chief Medical Officer, and Erik Harris, Chief Legal Officer. I would like to remind investors that this call will include forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the types of statements identified as forward-looking in our 2019 These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks relating to our business, see our periodic reports filed with the SEC.

Well below.

[music].

Okay.

[music] yeah.

I'd.

[music] yet is 94.

Hi, Yes can you hear me.

[music].

Background.

[music].

Let's see there's something going on in the background.

Yes.

Greetings.

[music], sorry, I don't really have another way that sweats audio I have 10, I can give you any of them here at <unk> nine or <unk>.

Bye now.

[music].

Catherine with the.

[music].

Emil D. Kakkis: I'll now turn the call over to Emil. Thank you, Danielle, and good afternoon, everyone, and thank you for joining us on today's call. Ultragenyx had a good first quarter despite everything going on. The impact of the COVID-19 pandemic has been felt by everyone at Ultragenyx, the patients we serve, their families, and their health care providers. This is a truly unique point in the history of our society when everyone...

I E R.

[music].

Ladies and gentlemen, thank you said it by Watson to the Ultragenyx first quarter 2020 financial results conference call at this time, all because our listen only mode.

Emil D. Kakkis: High focused on their own, taking precedence over virtually everything else. When facing this pandemic, the need for a robust and effective biopharmaceutical industry has never been more clear. The pharmaceutical industry has mobilized its expertise to develop assays, drugs, and vaccines in dramatic ways. We are encouraged by the progress we are seeing. Although Ultras is not directly working on a COVID vaccine, last year we invested in and supported our mRNA therapeutic partner, Arcturus Therapeutics, which is developing an mRNA-based vaccine for COVID. They recently announced potentially important positive preclinical data for the mRNA COVID vaccine candidate, showing that it is potent at inducing a COVID-19 virus neutralizing immune response at a very low dose. The Arcturus mRNA vaccine program is unusual because it uses self-replicating RNA technology that both amplifies spike protein expression to induce an adaptive immune response and also stimulates the innate immune system better.

Please be about today's conference maybe recorded.

If you acquire any further systems. Please press star zero.

I'll now hand, the call if she's people today with Daniel Keatley.

Please go ahead.

Oh.

Noon and welcome to the Ultragenyx pharmaceutical financial results in corporate update conference call for the first quarter 2020.

We issued a press release detailing our financial results, which you can find on our website at Ultragenyx Dot Com I'm, Danielle Keatley senior director of Investor relation joining me on the collar email Cacace, Chief Executive Officer in President, Tony Sharp, Chief Financial Officer, Camille Bedrosian Chief Finance.

Officer, and Eric Harris, Chief Commercial officer.

I would like to remind investors. This call will include forward looking statements within the meaning of the safe Harbor provision the private Securities Litigation Reform Act at 1995, including but not limited to the types and statements identified as forward looking in our 2019 annual report on form 10-K that was filed on February 14 2020 are.

Emil D. Kakkis: We look forward to data from their clinical study, which is expected to initiate this summer. For our own products in the pandemic, we're continuing to do whatever is needed to support our patients. We've worked to ensure our patients treated with Cuspida and Mepsevi, as well as those participating in our clinical studies, continue to receive the treatments that they need during this challenging time. To date, only a relatively small fraction of our established commercial patients have had any issue with access. Fortunately, more than 8% of our CRESCITA patients already receive their care at home via a visiting nurse. This was established at the time of want to be convenient for patients and is lessening the potential impact of institutional clothing.

Quarterly report on form 10-Q that will be filed June and our subsequent periodic reports filed with the FCC, which will all be available on our website in the Investor section.

These forward looking statements represent our views only as of the data this call uninvolved potential 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.

Emil D. Kakkis: A few patients have needed help with their side of care, which our team is helping to resolve. One example of our efforts for the small number of patients that do need our assistance is the work our teams are doing with payers and the temporary authorization to provide self-administration of CRISPR as an option where in-home nurse administration is not feasible. On the clinical development front, we are able to move our gene therapy programs forward, but there are some limitations on the data we can collect for those already treated. We've paused the enrollment of the prophylactic steroid cohort in the DTX-301 program for OTC due to institutional closing. That said, we are ready to go once they open.

As well as risks relating to our business PR periodic reports filed with the FCC I'll now turn the call over to him.

Thank you Daniel.

Good afternoon, everyone and thank you for joining us on todays call.

Oh, Chuck had a good first quarter, despite everything going on.

Packing Cobot 19 pandemic bumping everyone Ultragenyx patients, we serve their families and their health care providers.

The truly unique point in history of our society with everyone highly focused on their own.

<unk> cross into were virtually everything else.

Basin with pandemic the need for a bus and effective bio pharma industry has never been more clear.

The biopharm industry as mobilize his expertise to develop assay drug vaccines and dramatic way. We're encouraged by the progress we are seeing.

Emil D. Kakkis: Enrollment, and Program, as well as other presentations about earlier stage and technology programs. For the ASO Clinical Program to treat Angeman, our partner, Genetics, has progressed to the clinic with GTX-102 and enrolled two patients who continue to receive treatment. Further progress will depend on access at sites, and our partner Genetics is working to push the program forward in a safe manner. While COVID-19 has created a unique set of challenges, we are taking, Unknown Speaker, Unknown Attendee, Unknown Attendee, Unknown Attendee, Thank you, Emil. During these extraordinary times, I am extremely grateful for the relentless work the commercial and medical teams do every day on behalf of patients. Our commercial team is especially focused on ensuring the continuity of patient care.

Although I'll just not directly working on a club indexing last year, we invested in and supported our m. already therapeutic partner or toward therapeutics.

Bumping and more in a big vaccine for coated.

They recently now potentially important positive preclinical data for the M. ornate cobiz vaccine candidate showing that is a potent at inducing a cobot 19 virus neutralize immune response at very low dose.

They are tourism Arnie vaccine problems unusual because it usually sell for upgrading our in eight technology that both amplifies like protein expression to induce an adaptive immune response and also stimulate.

We need in system better.

We look forward to data from their clinical study expected initiate this summer.

For our own product in the pandemic, we're continuing to do whatever is needed to support our patients.

We work to ensure a patient treated could be done met savvy as well those participating in our clinical stage continue to receive the treatments that they need during this challenging time.

Emil D. Kakkis: Since launching CrisVita in April 2018, we have grown the patient base significantly, and our top priority is to ensure that these patients continue receiving the Important Clinical Benefits of this therapy. During this COVID-19 period of social disruption, we're seeing a small number of patients who are not able to go to their site of care for treatment, where a specialty pharmacy has worked with a payer to allow for self-administration. These are exceptions that have been initiated by the patient and their healthcare provider in response to a specific concern about COVID-19 exposure. In North America, through the first part of this year, we have seen continued strong demand for Crisvita. More than 80% of patients receive the procedure through at-home nurse administration, which has helped to minimize any COVID-related disruptions. As one would expect,

To date, only a relatively small fraction of our established commercial patients have had any issue with access.

Fortunately more than 80% of or Chris either patients already received their care at home by visiting nurse.

This is established at the time of wants to be convenient for patients and is lessening the potential impact of institutional closings now.

You patients have need help with decided care, which are team is helping to resolve.

One example of our efforts with a small number of patients that do need our system is the worker teams are doing with payers EMEA temporary authorization to provide self administration of Chris feed as an option work in home nurse administration is not feasible.

On the clinical Bowman front, we're able to move our gene therapy program forward, but there are some limitations on the data we can collect for those already treated.

Erik Harris: Social distancing will present some challenges for new patients to receive a diagnosis and start Crispida therapy. We are being respectful and understanding of the additional burdens this pandemic has put on health care providers. It has required our team to come up with new and innovative ways to safely educate these providers on our products. Our field teams are conducting virtual speaker programs to educate a national audience of patients and caregivers. We are also hosting national webinars for healthcare providers that will be led by prominent KOLs. Lastly, we have expanded our suite of digital tools and used these resources to maintain close contact with our health care providers as they continue to actively manage their patients with XLA. We believe these types of efforts will support our initiatives around generating new start, Outside of North America, we continue to have meaningful discussions with regulatory and reimbursement agencies, while also supporting increasing demand for named patient therapy. In Colombia and Argentina, we continue to receive positive feedback and see steady demand as the number of patients on reimbursed named patient treatment continues to increase. In Brazil, we have seen a steady number of requests for Prifida, with many of these patients filing legal injunctions to be able to receive the therapy.

We paused enrollment of the prophylactic Jerry cohort in the DTA real one program for Otcs due to institutional closing.

That said, we are ready to go once the open and.

Enrollment.

The program as well the other presentations about earlier stage and technology program.

For the air So clinical program to treat arrangement our partner genetic has progressed to the clinic with Gtx, one or two enrolled two patients who continue to receive treatment.

Further progress will depend on access at site and our partner genetics is working to push the program forward in a safe manner.

Well covered 19 has created a unique set of challenges we are taking steps necessary to ensure our commercial patients continue receiving their therapy or discussion you asked a few remain on schedule and our clinical and preclinical programs continue to generate data.

With that I'll turn the call to Eric who will provide a commercial update highlighting the strength of our core business and what it seems to expand our global reach.

Thank you able.

During these extraordinary times I am extremely grateful for the relentless work the commercial medical teams do everything on behalf of patients.

Commercial team is especially focused on ensuring the continuity of patient care.

Since launching Chris FIDA in April 2018, we have grown to patient base significantly in our top priority is to ensure that these patients continue receiving the important clinical benefits of this therapy.

Erik Harris: This has resulted in a growing number of patients who have been treated with Crisvida after successfully negotiating the judicial review process. Earlier in the year, we had positive discussions with the Ministry of Health seeking to obtain full pricing and reimbursement approval. The COVID-19 situation forced the agency to shift its focus and put our discussions on hold. But they are still reviewing new patient requests, and allowing patients with XLH to be treated with Crisvita. Based on these interactions and the increasing demand, we are confident that Brazil remains a significant opportunity for CRISPVIDA in Latin America. Similarly, in Turkey, demand for Crisvita continues to grow as more patients are successfully being granted injunctive, FIFIDA is an important part. Thank you very much.

Joined us to covert 19 period of social distancing.

We're seeing a small number of patients who are not able to go to their site of care treatment.

Aware of a handful of instances, where specialty pharmacy has worked with the payer to allow for self administration. These are exceptions that had been initiated by the patient.

Their health care provider in response to a specific concern about cobot 19 exposure.

In North America through the first part of this year, we're seeing continued strong demand for Christina.

More than 80% of patients receive for Sveta through at home Nurse administration, which has helped to minimize any covert related disruptions.

Erik Harris: Moving to UX007, we are continuing to prepare for a potential approval for this therapy for patients with long-chain fatty acid oxidation disorders by the PDUFA date of July 31, 2020. Based on the data from our clinical studies and feedback from physicians and patients, we believe UX007 fills a significant unmet need and that there are a substantial number of patients who could benefit from UX007 despite current treatment options. With the advent of newborn screening for LC-FAOD in the U.S., many of the 2,000 to 3,500 estimated patients are already diagnosed, and the majority of patients are seen at approximately 160 of the major metabolic centers across the country.

As one would expect.

So distancing will present, some challenges for new patients to receive diagnosis and start because we didn't therapy, we are being respectful and understanding of the Alberta.

This pandemic has put on health care providers, because required our team to come up with new and innovative ways to safely educate these providers on our products.

I feel teams are conducting virtual speaker programs.

Okay, the national audience of patients and caregivers.

We're also seeing national Webinars for health care providers that will be led by prominent crude oil.

Lastly, we have expanded our suite of digital tools and used these resources to maintain close contact with health care providers as they continue to actively manage their patients with XL late.

We believe these types of efforts will support our initiatives around generating you start for.

Outside of North America continue to have meaningful discussions with regulatory and reimbursement agencies, while also supporting increasing demand for named patient therapy.

Shalini Sharpe: Our existing commercial efforts with Crisvita and Mevsevi have helped build strong relationships with these metabolic systems, which will be instrumental in the launch of UX007. Given this significant overlap with our current commercial activities, we will be able to leverage much of the current infrastructure and only modestly increase our existing field. Looking forward, we have two potential approvals coming later this year. We expect there to be significant interest in UX007 for LC-FAOD and Crisvita for TIO if they are approved. These launches will build steadily over time, all the while bringing important therapies to patients with few options. We are excited for what could be our third or fourth rare disease launch in less than three years. We plan to utilize our collective experience to ensure our continued success. With that, I'd like to turn the call over to Shalini, who will walk you through the financial results for the quarter. Thank you, Erik, and good afternoon, everyone. Earlier today, we issued a press release that included a financial update, which I will briefly summarize. Total revenue for the three months ending March 31, 2020 was $36.3 million.

Colombia in Argentina, we continued to received positive feedback and see steady demand as the number of patients on reimbursed.

Name patient treatment continues to increase.

In Brazil, we have seen a steady number of request for Chris feeder with many of these patients filing legal injunctions to be able to receive the therapy.

This has resulted in a growing number of patients who have been treated with Chris meter after successfully negotiating the judicial review process.

Earlier in the year, we had positive discussions with the ministry of health seeking to obtain full pricing and reimbursement approval.

Cobot 19 situation force the agency to shifted focus and put our discussions on hold.

But they are still reviewing new patient requests, allowing patients with XL age to be treated with Chris Vito.

Based on these interactions and the increasing demand we are confident there Brazil remains a significant opportunity for Chris FIDA in Latin America.

Similarly in Turkey demand for Chris Meta continues to grow as more patients are successfully being granted junctions.

Shalini Sharpe: In the first quarter of 2020, total Crisvita revenue was $31.4 million. This included $27.2 million in collaboration revenue in the North American Profit Share Territory and net product sales in other regions of $1.6 million, or a total of $28.8 million in the Ultragenyx Territory. Non-cash royalty revenue related to the sales of CRISPRIDA in the European Territory was $2.6 million.

Chris FIDA is an important part of therapy for patients with XL age and we believe we will receive reimbursement approval for named patient sales based on the strength of our clinical data and positive discussions we've had with Turkish officials in the first quarter of Twentytwenty.

Shifting to you X O seven.

We're continuing to prepare for a potential approval for this therapy for patients with long chain fatty acid oxidation disorders by the could do for date of July 31 Twentytwenty.

Shalini Sharpe: Recall that the rights to the royalties in this region were sold to Royalty Pharma in December of 2019. MFSEBI product revenue for the first quarter of 2020 was $3.4 million, and UX-007 named patient revenue was $1.4 million. Our total operating expenses were $157 million for the first quarter of 2020. This includes $25 million which was paid to Genetics to maintain our option to acquire the company after their IND for GTX-102 was accepted by the U.S. FDA. This also includes $20.2 million of non-cash stock-based compensation.

Based on the data from our clinical studies and feedback from physicians and patients. We believe you X O seven fills a significant unmet need that there are substantial number of patients who could benefit from you X O seven despite current treatment options.

With the advent of newborn screening for LC failed D. In the U.S. Many of the 2002 3500 estimate of patients already diagnosed.

The majority of patients are seen at approximately 160 of the major metabolic centers across the country.

Existing commercial efforts with Chris Vito and MEP savvy have helped build strong relationships with these metabolic centers.

Shalini Sharpe: Our R&D costs were $113 million. We expect our R&D costs to increase moderately over time as we continue advancing product candidates from early preclinical development into early and pivotal clinical studies. Our SG&A costs in Q1 were $47.5 million.

Which will be instrumental in the launch of you X all seven.

Given this significant overlap with our current commercial activities, we will we will be able to leverage much of the current infrastructure and only modestly increase our existing field force.

Looking forward, we have two potential approvals coming later this year, we expect there to be significant interest you X all seven four LC facility and Chris meter for T. Io if they are approved.

Shalini Sharpe: We expect SG&A to increase moderately over time as we support our commercial programs and potential new product launches. Our cost of sales was a negative $3.5 million for the first quarter of 2020, which included a credit of $4.6 million that was agreed to during the quarter by one of our manufacturers due to previously produced inventory batches of Mepsevi that did not meet our quality standards. As a reminder, the company had previously recorded a reserve of $5.7 million for these batches during the year ended December 31, 2019. However, we do not anticipate any supply interruptions or future reserves related to this particular issue at this time. Net loss for the quarter ended March 31, 2020, with $119 million or $2.05 per share of basic and diluted, compared with a net loss of $96.8 million or $1.82 per share of basic and diluted for the first quarter of 2019.

These launches will build steadily over time, all the while bringing important therapies to patients with few options.

We are excited for what could be our third and fourth rare disease launches in less than three years, and we plan to utilize our collective experience to ensure our continued success.

With that I'd like to turn the call over to Shalini, who will walk you through the financial results for the quarter.

Thank you Eric and good afternoon, everyone.

Earlier today, we issued a press release that included a financial update which I will briefly summarize.

Total revenue for the three months ending March 31st 2020 with $36.3 million.

In the first quarter 2020, total Chris Webster Bank revenue was $31.4 million.

Include $27.2 million in collaboration revenue in the North American profit share territory, and net product sales and other regions of $1.6 million or a total of $28.8 million and Ultragenyx territory.

Noncash royalty revenue related to sales of Kristina in the European territory was $2.6 million recall that the rights to the royalties in this region were sold to royalty pharma in December 2019.

Shalini Sharpe: The net loss in the first quarter of 2020 includes a $7.7 million unrealized gain from the Fair Value Adjustment on the investment in Arcturus Equity Securities and $8.1 million in non-cash interest expense on a liability related to the sale of future royalties. In the first quarter of 2020, cash use and operations was $95.2 million. We ended the quarter with $705 million in cash and cash equivalents and available for sale investment. This includes $75 million from the Daiichi Sankyo Common Stock Purchase, which closed in March of 2020, but excludes the $125.6 million receivable from the Daiichi Sankyo Strategic Manufacturing Partnership upfront payment. These funds were received in April of 2020. Moving to our guidance for 2020, we are currently maintaining the guidance range that we shared at the beginning of the year. Specifically, Krispita revenue to Ultragenyx in our territories is expected to be between $125 and $140 million.

That's 70 product revenue for the first quarter of 2020 was $3.4 million and you exit was seven named patient revenue was $1.4 million.

Total operating expenses were $157 million for the first quarter 2020.

This includes $25 million, which was paid to genetics to maintain our option to where the company after their eye Andy for Gtx, one or two was accepted by the U.S. FDA.

Also includes $20.2 million, a noncash stock based compensation.

Our R&D costs were $113 million.

We expect our R&D cost increased moderately overtime as we continue advancing product candidates from early preclinical development into early in pivotal clinical study.

Our SGN a cost in Q1 were $47.5 million.

We expect SNH increased moderately overtime as we support a commercial programs and potential new product launches.

Our cost of sales was a negative $3.5 million for the first quarter of 2020, which includes a credit a $4.6 million that was agreed to during the quarter with one of our manufacturer due to previously produced inventory that isn't that savvy that did not meet our quality standards.

Shalini Sharpe: Those territories include North America, Latin America, and Turkey and exclude the EU royalty, as this was monetized in the transaction that was completed with Royalty Pharma that was announced in December of 2019. We also continue to expect the pace of our revenue growth to significantly exceed the pace of expense growth and therefore maintain our projection of a greater than 20% decrease in net cash burn, which includes net cash used in operations as well as capital expenditures. As the COVID-19 pandemic evolves, we will continue to look at the potential impacts on our business, including this guidance range, and will provide updates when or if they become material. With that, I'd like to turn this call over to Camille, who will provide an update on some of our recent regulatory interactions and clinical programs. Thank you, Shalini. I, too, wish everyone a good afternoon.

As a reminder of the company had previously recorded a reserve of $5.7 million for these batches. During the year ended December 31st train 19th we.

We do not anticipate any supply interruption or future reserves related to this particular issue at this time.

Net loss for the quarter ended March 31st 2020 was $119 million or $2.05 per barrel per share basic and diluted compared with a net loss of $96.8 million or $1.82 cents per share basic and diluted for the first quarter between 19.

The net loss in the first quarter of 2020 includes a 7.7 million dollar unrealized gains and the fair value adjustment on the investment in Arcturus equity security and $8.1 million in noncash interest expense on the liability related to the fail a future royalties.

In the first quarter 2020 cash used in operations was $95.2 million.

We ended the quarter with $705 million and cash cash equivalents and available for sale investment.

Camille L. Bedrosian: I will discuss our progress with our two programs currently under regulatory review and will provide an update on the Angelman Syndrome program. Starting with UX007 for long-chain fatty acid oxidation disorders, or LCFAOD, a devastating disease with significant morbidities despite newborn screening and current use of even-chain MCT oil. The FDA is currently reviewing the new drug application and has set a PDUFA date of July 31, 2020. The review process continues on track, and we expect a review decision by that date. Importantly, all of the anticipated clinical and manufacturing inspections for UX007 have been successfully completed.

This includes $75 million from the Daiichi Sankyo common stock purchase which closed in March or 2020, but excludes the $125.6 million receivable from the Daiichi Sankyo strategic manufacturing partnership upfront payments. These funds were received an April 2020.

Moving to our guidance for 2020, we're currently maintaining the guidance range that we shared at the beginning of the year.

Specifically Kristina revenue to Ultragenyx in our territories is expected to be between 125 and $140 million.

Those territories to include North America, Latin America, and Turkey, and exclude the EU royalty as this was monetized in the transaction that was completed with wealthy pharma that was announced in December of 2019.

We also continue to expect the pace of our revenue growth to significantly exceed the pace of expense growth and therefore maintain our projection of greater than 20% decrease in net cash burn which includes net cash used in operations as well as capital expenditures.

Camille L. Bedrosian: At this point, we do not believe that any additional inspections would be required for completion of FDA's review. In addition to the progress in the U.S., a marketing authorization application is under review by regulatory authorities in Brazil, and we continue discussions with regulatory authorities in the EU and Canada. Based on our experience, we know that many patients with LCFAOD are not doing well on current management with even-chain MCT oil and are seeking new treatment options. We have seen this interest through the significant number of requests for Compassionate Access and our Named Patient Program. Moving to CUSVITA for tumor-induced osteomalacia, or TIO, a rare debilitating disease for which approximately half of patients have tumors that cannot be surgically removed, leaving them with no other current treatment option.

At the Kobin 19 pandemic evolves, we will continue to look at the potential impacts to our business, including this guidance range and will provide updates when or if they become material.

With that I'd like to turn this call over to Camille who will provide an update on some of our recent regulatory interactions and clinical program.

Thank you Shalini I to wish everyone a good afternoon.

We will discuss our progress with our two programs currently under regulatory review and will provide an update on the increments syndrome program.

Starting with you ekso of seven for long chain fatty acid oxidation disorders, or LCFS <unk> D. A devastating disease with significant morbidities. Despite newborn screening and current you said even chain and see cheap oil.

The FDA is currently reviewing the new drug application and to set up to do for date of July 31 2020.

Camille L. Bedrosian: Erik previously discussed our commercial progress with Crisvita, and I am encouraged that we are moving closer to a second potential approval for this medicine for the treatment of patients with TIO. This would be the first FDA-approved treatment for patients with this devastating disease and the setting of an unresectable tumor. The review of our supplemental BLA is on track for a decision by the PDUFA date of June 18, 2020. We continue conversations with the FDA, and we do not anticipate that inspections would be required for completion of their review. I will now touch on our program with Genetics Biotherapeutics to advance GTX-102, an antisense oligonucleotide for the treatment of Angelman syndrome. Angelman Syndrome is a devastating neurological disease that affects approximately 60,000 patients worldwide, and there are no approved treatment options today.

They review process continues on track and we expect to review decision by the PDUFA date.

Importantly, all of the anticipated clinical and manufacturing inspection for you actually below seven had been successfully completed.

At this point, we do not believe that any additional inspections would be required for completion of ft A's review.

In addition to the progress in the U.S. a marketing authorization application is under review by regulatory authorities in Brazil, and we continue discussions with regulatory authorities in the EU and Canada.

Based on our experience, we know that many patients with L.P.F.L.D. are not doing well on current management with even chain MCT oil and are seeking new treatment options. We've seen this interest to the significant number of request for compassion access and our named patient program.

Moving to could feed us for tumor induced osteomalacia or T O a rare debilitating disease for which approximately half of patients have tumors that cannot be surgically removed, leaving them with no other current treatment options.

Camille L. Bedrosian: The disease is a neurodevelopmental disorder and not neurodegenerative, so there is potential to reverse many of the disease manifestations, which include speech and cognitive impairment, seizures, ataxia, and sleep dysfunction. We believe that the team at Genetics has developed a very potent and specific, differentiated antisense oligonucleotide, an approach that can directly target the disease. In addition, they have done a tremendous job of moving the program into the clinic rapidly and efficiently.

Eric previously discussed our commercial progress with Christina and I'm encouraged that we are moving closer to a second potential approval for this medicine for the treatment of patients with T. Io.

This would be the first FDA approved treatments for patients with this devastating disease and the setting up an on resected tumor.

The review of our supplemental B.L.A. is on track for a decision by the PDUFA date of June 18 2020.

Camille L. Bedrosian: The first cohort of the Phase I-II study has been enrolled, and the two patients continue through dose escalation. Continued progress through the cohorts will depend on institutional status for continued safe study conduct. Earlier this month, GTX 102 was granted fast track designation by the FDA.

We continue conversations with the FDA and we do not anticipate that inspections would be required for completion of there with you.

I will now touch on our program with genetics biotherapeutics to advance Gtx, one or two and antisense oligonucleotides for the treatment of Angelman syndrome.

Camille L. Bedrosian: This designation will help facilitate the expedited development and review of this potential therapy for patients with this devastating disease. While we continue to track the potential impact of the COVID-19 pandemic on site activation and data collection, the team is making good progress, and we expect preliminary data from this study in the first half of 2021. As you can see, we are making significant progress on the regulatory side and could have approvals for two new indications in the coming months, bringing important therapies to patients who are waiting and who do not have adequate treatment options today. Furthermore, the Angelman Syndrome Program has moved into the clinic, and the team continues to do a tremendous job advancing this program. With that, I will now turn over the call to Emil. Thank you, Camille.

Angelman syndrome is a devastating neurological disease that affects approximately 60000 patients worldwide and there are no approved treatment options today.

The diseases at Neurodevelopmental disorder, and not neuro degenerative. So there is potential to reverse many of the disease manifestations, which include speech in cognitive impairment.

Seizures ataxia and sleep dysfunction.

We believe that the team at genetics has developed a very potent and specific differentiated antisense oligonucleotides an approach that can directly target the disease.

In addition, they have done a tremendous job of moving the program into the clinic rapidly and efficiently.

The first cohort of the phase one two study has been enrolled and the two patients continues to dose escalation.

Emil D. Kakkis: I will discuss our gene therapy programs and then we'll move on to your questions. Starting with DTX-301, our gene therapy for the treatment of Ornithine Transcarpamylase Deficiency, or OTC. OTC deficiency is an X-linked urea cycle disorder that limits the body's ability to detoxify ammonia in urea, and these patients can quickly be treated in a full medical, causing body deficits, osculation, coma, and, in some cases, death. At the beginning of this year, we reported positive data from dose cohort three and longer-term data from the first two cohorts of our In cohort three, we're seeing response from all three patients, and we believe this higher dose has achieved a consistent response and an adequate level of therapeutic effect. In total, up to six of the nine patients that he has treated have responded, and importantly, three patients have come off their ammonia scavenger medication and liberalized their diet.

Continued progress through the cohorts will depend on institutional status.

For continued say study conduct.

Earlier this month Gtx, one or two was granted fast track designation by the FDA.

This designation will help facilitate the expedited development and review of this potential therapy for patients with this devastating disease.

Well, we continue to track the potential impact of the covert 19 pandemic on site activation and data collection. The team is making good progress and we expect preliminary data from this study in the first half of 2021.

As you can see we're making significant progress on the regulatory side and could have approval for two new indications in the coming months, bringing important therapies to patients who are waiting and who do not have adequate treatment options today.

Furthermore, the Angelman syndrome program has moved into the clinic and the team continues to do a tremendous job advancing this program.

Emil D. Kakkis: We consider these patients complete responders, and these patients appear to be metabolically cured. At next week's American Society of Gene and Cell Therapy conference, or ASGCT, we will present updated data from the first three cohorts of this study and plan to hold an investor conference call after the ASGCT presentation to discuss both the OTC and GSD-1A data updates. For the OTC program, we plan to enroll a fourth cohort at the same dose as Cohort 3, but using prophylactic steroids rather than reactive steroids to potentially enhance the level of expression and provide more consistent expression. We've identified patients for COVID.

With that I'll now turn over the call to anymore.

Thank you for meal.

I will discuss our gene therapy programs and then we'll move on to your questions.

Starting with Dts Threeo, one being therapy for the treatment warranted the transcript families deficiency or PC.

So to see the businesses X linked urea cycle disorders limits, the body's ability to detoxify ammonia urea.

And these patients.

Well, Matt this is causing budget deficit.

Coma in some cases, Jeff.

At the beginning this year, we reported positive data from dose cohort three and longer term data from the first two cohorts of our own study.

Emil D. Kakkis: The COVID-19 pandemic, we're waiting to dose these patients because of the closure of institutions, as well as the potential risk to patients, especially those using steroids. At this point, we still expect data from this cohort in the second half of 2020, barring significant further delays related to COVID-19. We are also simultaneously planning our regulatory meetings and the phase 3 study, and we expect to meet for an end of phase 2 meeting with the FDA based on the first three cohorts alone. Based on our ongoing conversations with the FDA, we expect that ammonia will be a primary endpoint. The FDA considers ammonia a validated clinical endpoint, and they have approved other products based on it. The Phase III study is currently expected to begin enrolling patients in the first half of 2021.

In cohort three we're seeing response from all three patients who we believe this higher doses achieved a consistent responds an adequate level of therapeutic that.

Total up to six of the nine patients that have responded and importantly, three patients have come off their ammonia scavenger medication liberalize their diet.

We consider the patient complete responders in these patients appeared to be met above the cure.

And next week.

Second study the gene and cell therapy conference.

You see tea, we will present updated data from the first three cohorts of the study plan to hold Investor Conference call. After the GTT presentation, just got both the LTC and GLP one they did update.

For the OTI see program, we plan to enroll a fourth cohort at the same doses cohort three but using prophylactic steroid rather than reactive steroids to potentially enhance the level of expression and provide more consistent expression.

Emil D. Kakkis: Moving to DTX-401, our Glycogen storage disease type 1a, a disease that leads to severe and sometimes life-threatening hypoglycemia. Patients with GSD-1A today have to take chlorhexidine every three to four hours, which can keep glucose levels stable, But it does not address the disease and its long-term complications, and patients or their parents live in fear of death if they miss a single cornstarch out.

The identified patients for the for coal.

The other cobot 19 pandemic, we're waving your dose these patients do the closure institutions as well as a potential risk patients, especially those using steroids.

At this point, we still expect data from this cohort in the second have 2020 barring significant further delays related to cope with 19.

We're also simultaneously planning a regulatory meetings and the B B study and we expect to meet corn and that the team meeting with FDA based on the first recall work well.

Emil D. Kakkis: Today, we've shown data from the first two cohorts with all six patients demonstrating a meaningful clinical response to therapy at 2E12 and 6E12 genocopies per kilo dose levels, including a substantial decrease in the required dose of corn starch. Doho will have a respiratory cohort of three patients at the same dose in December and are planning to schedule the FDA for the phase 3 study. We will share the available data from the confirmatory cohort at the ASGCT meeting next week. While some of the later patient site visits in Cohort 3 did not occur due to COVID-19, we expect to be able to share data from the site visits that did take place, as well as corn starch reduction data, which should not require a visit.

Based on our ongoing conversation was F.D.A., we expect that ammonia will be a primary endpoint.

You have to consider the ammonia validated clinical endpoints and they have proved other product based on ammonia.

The phase three studies currently expecting to begin enrolling in the first half 2021.

Moving to Dth for a one RG <unk>.

Glargine store type one a these leases that you're in sometime like Brendan but im yeah.

Patients with GLP, one eight today have to take corn, Jeffrey vehicle hours, which can keep glucose level.

But it does not address the disease in the long term complications and patient or their parents live in fear of death.

Just a single cornstarch, though.

Today, we have shown data from the first you cohort lasik patients demonstrating a meaningful clinical response to therapy it to eat 12, and six each well gee copies.

Emil D. Kakkis: In addition, continuous glucose monitoring was introduced into the protocol for this third conformatory cohort, and we'll be able to share insights from the available continuous glucose monitoring that is conducted at home. Pending these data and the expected end of Phase 2 meetings with FDA, we could be in a position to begin the Phase 3 study by the end of the year, depending on whether there are any further delays. At the end of March, we entered into a strategic partnership with Daiichi Sankyou and granted them a non-exclusive license for our gene therapy manufacturing technology, including our HeLa platform. Daiichi Sankyou is building their gene therapy program as a key part of their 2025 vision, and this new partnership shows their interest in our HeLa producer cell line platform, in particular, that we believe is the most scalable mammalian AV Daichi Fenke made an upfront payment of $125 million in cash and a $75 million equity investment in Ultragenyx.

Hello dose levels, including a substantial decrease in the required dose of corn starch.

Just a takeover of treat patients at the same Dover dose.

And our plan discussion with you about the phase three study.

We will share the available data from the confirmatory cohort at the GCG meeting next week.

Well some of the later patient site is the record three did not occurred due to cope with 19.

Expect to be able to share data from the signs that did take place as well as corn starch production data and should not required to that in addition, continuous glucose monitoring wasn't just into the protocol for the third confirmatory cohort will be able to share insights from available continuous glucose monitoring that conducted at home.

Pending these data and directed into FY two meetings that we could be in a position to begin the phase three study by the end of year, depending on whether there are any further delays.

At the end of March we entered into a strategic partnership with Daiichi Sankyo and granted them a nonexclusive license for gene therapy manufacturing technology, including our he will platform.

Thank you with building their gene therapy program as a key part of their 2025 vision and this new partnership shows the interest in our he left producers cell line platform in particular.

Emil D. Kakkis: In addition, Daiichi Sanka will pay $25 million upon completion of the technology transfer of the HELA, CL, and HEK-293 forms, as well as single-digit royalties on net sales of products manufactured in either system. I will also point out that this is non-exclusive, and we look to build other collaborations around our AAV technology over time. I'll briefly recap our major milestones in the coming months that will continue to drive our progress, and then we can move to the Q&A. Chris Vita, we believe we're still on track to achieve revenue between 125 to 140 million in North America, Latin America, and Turkey.

So we believe the most scalable mammalian Avi manufacturing system into 2000 leaders of suspension culture.

Great mandate, you think you made an upfront payment of 125 million in cash and a $75 million reinvestment ultragenyx.

In addition, Daiichi Sankyo will pay 25 million upon completion technology transfer particular, Seattle cheeky to nine three warm.

As low single digit royalties on net sales of products manufactured in either system.

Also pointed out this is not inclusive and we look build other collaborations around or Avi technology overtime.

I'll briefly recap our major milestones in the coming months that will continue to drive our progress and then we can move to the human error.

Chris speed.

We believe we're still on track to achieve revenue between 125 to 140 million North America, Latin American Turkey. This will be driven by continued good performance in both the U.S. in Canada and expansion or reach in Latin American Turkey over time.

Emil D. Kakkis: This will be driven by continued good performance in both the U.S. and Canada and expansion of reach in Latin American Turkey over time. Well, we have seen minimal impact from COVID-19 so far. However, the crisis does continue and could impact the business.

Well, we have seen minimal impact from cobot. Thank you. So far the crisis does continue it could impact the business will continue our special efforts to support established patients and new patients during that time.

Emil D. Kakkis: We'll continue our special efforts to support established patients and new patients during this time. In addition, we're looking to expand proceeds to treat TIO, a small patient population but one with a very urgent need for treatment. If approved in this indication, we believe CRISPRIDA will be preferred over phosphate therapy.

In addition, we're looking to expand crazy the treaty Io small patient population, but one was very urgent need for treatment.

Approved in this indication we believe could speed it would be preferably adopted work basi therapy.

For us so seven or in the review is on track and that decision by the PDUFA date of July three for 2020, we're currently in launch preparation or to be able to begin African easily following approval.

Emil D. Kakkis: For UX007, our NDA review is on track, and we expect a decision by the PDUFA date of July 31, 2020. We are currently in launch preparation, or we may be able to begin efforts immediately following approval. For the gene therapy programs, we've shown positive data on many respondents from both our two programs in OTC and GSD 1A. We'll share data from both programs next week at the ASGCT conference. Our program for Wilson's disease also continues to progress in an IND as expected by the end of 2020, provided the COVID-19 pandemic does not cause any delays in non-clinical or manufacturing activities. This program will be the second clinical program to utilize the company's HeLa manufacturing system in the clinic. GTX-102 ASO Program for Angelman Syndrome also continues to advance, with the first cohort dose and additional cohorts planned.

For the gene therapy program, we've shown positive did on many responsible or two programs and PC and GLP one a we'll share data from both programs next week at the is GCT conference.

Our program for Wilson. These also continues to progress in an idea is expected by the end of 2020 revise its over 19 pandemic does not cause any delays nonclinical our manufacturing activities.

This program will be the second clinical program to utilize the Companys ULA manufacturing system in the clinic.

Gtx, one or two is so program for enjoyment Sintrom also achieved advances the first core dose initial cohort plan, we expect to provide preliminary data in the first half 2021.

Emil D. Kakkis: We expect to provide preliminary data in the first half of 2021. As you can see, we continue to make significant progress on the commercial, clinical, and business development fronts, even during these challenging times. We have built a strong, resilient business, leveraging traditional and non-traditional finance. While everyone is feeling the impact of COVID-19, we believe we are well positioned to continue delivering important therapies to patients in need. I'll stop there.

As you can see continued to make significant progress on the commercial clinical and business development front, even during these challenging time.

We built a strong resilient business leveraging traditional and nontraditional financing.

I want to feeling the impact Koeppen 19, we believe we are well positioned to continue delivering important therapies to patients in need.

I'll stop here, let's move to your question.

Operator: Let's move to your questions. Operator, can you please provide the instructions for the Q&A portion of the call? Thank you. Ladies and gentlemen, as a reminder to ask a question, you need to press star 1 on your telephone. To withdraw your question, please press the pound sign.

Operator can you please provide instructions for the Q and a portion of the call.

Thank you.

Ladies and gentlemen, RASM I was asked the question you depressed bar one on your telephone to withdraw your question. Please press the pound cake.

Operator: We do ask that you limit yourself to one question and one follow-up. Please stand by while we call a Q&A round. Our first question comes from Yaron Werber of Cowling, Orlando, D.C. Yeah, hi, thanks so much for taking my questions and, hopefully, you can hear me okay. So Emil, just a couple of questions on OTC and GSD-1A in terms of it sounds like we're going to get updates, you know, in a week from now at the conference. How are we looking to basically reconfirm the prior data, or are you thinking that the data can potentially get better? And then secondly, on GSD-1A, you won't be able to have all the data that you mentioned.

We do ask that you lived up to one question and one follow up.

Please standby, while the Kotalik you anywhere out there.

Our first question cost Myanmar Werber of Cowen Your line is open.

Yes, hi, thanks, so much for taking my questions and hopefully you can see you can hear me okay.

So it will just a couple of questions on OTI C and just the one a in terms. Although it does look we're going to get updates you know in a week from now at the conference.

How are we looking to basically reconfirm the prior data or are you thinking that is kinda data potentially get better and then secondly, an GST when they you won't be able to have all the data you mentioned, obviously patients could hospitalized no for the glucose monitoring so what data can we expect at that meeting and then.

Yaron Benjamin Werber: Obviously, patients can't get hospitalized now for glucose monitoring. So what data can we expect at that meeting? And if you don't mind, I have a quick follow-up. Share your own.

To show might have a quick follow up.

Sure your own obviously I'm not going to pre run the actual data. So what I'll tell you is it the ODC data, we're expecting is from the cohort that you've already seen.

Emil D. Kakkis: Obviously, I'm not going to pre-run the actual data. So what I'll tell you is that the OTC data we're expecting is from the cohort that you've already seen. There will be more data from this cohort. So that will just be further data on the existing cohorts that we announced earlier in the year. For GSD-1A, Cohort 3 has not been presented before, so that's new data on a new cohort, done at the same dose as Cohort 2, but it'll be three new patients, and they'll have a significant amount of data, though not all the data points, because some of the later ones were... [inaudible] that's what we're expecting. So more of an extension for cohort 2, but cohort 3 should be some new data.

We'll be more data from that cohort.

So that will just be further data on the existing cohort that we announced on earlier in the year rigidity. One age cohort three has not been presented before so that's new data and the new cohort.

Does the same doses cohort two.

But it would be a new three patients and they'll have.

The amount of data, though not all the all the data points because some of the later one were.

We could not connect but we think we have enough data to build the story and cohort three to the street. So that's what we're expecting so more of extension for code to the Coordthree should be some new data.

Okay, and then it sounds like you're gonna be going to talk to F.D.A. about the sort of the end of phase two.

Emil D. Kakkis: Okay, and then it sounds like you're going to talk to FDA about the end of Phase 2 or the pre-Phase 3 meeting. At that point, you probably will not have the fourth cohort of three patients on prophysteroids in OTC and, you know, it looks like you're going to have more follow-up in GSD1A, and hopefully, by that point, you'll get the glucose monitoring done as well.

Or the pre phase three meeting at that point, you probably will not have the fourth cohort of three patients on prophy steroids in LTC.

And.

You know he looks like you're going to have more follow up on just the one day and hopefully by that point, you'll you'll get the glucose monitoring done as well, but I guess my questions are as you sort of move into planning the phase three we're in both programs you might still sort of enhanced the dosing help us come to think about you don't know you don't want to hold the phase.

Yaron Benjamin Werber: But I guess my questions are, as you sort of move into planning the Phase 3, where in both programs you might still sort of enhance the dosing, help us kind of think about, you don't want to hold the Phase 3, but at the same time, you'll generate more data that can maybe even make the product, you know, even better suited for these patients. So is the thought to move to Phase 3 and then potentially do a protocol change later on with the latest doses, or are you thinking about it in a different way? Thank you. I understand.

Three but at the same time, you'll generate more data that can maybe even make what products you know even better suited for these patients. So is the thought to move to phase three and then potentially do a protocol changes later on with the latest those thing or are you thinking about announcement, yes. Thank you I understand. Thank you are on I, We would go with the phase you probably prefer in our expense.

Emil D. Kakkis: We would go with the Phase 3 probe we prefer, and our expectation of OTC is that we would go with a prophylactic steroid arm, I mean, design rather than a reactive steroid. There's been enough data in enough programs to say that prophylactic steroids probably work better than reactive steroids in general. We have enough safety information now to suggest that. So our plan is to put forth a prophylactic steroid approach. We would like, though, to confirm that this works well by testing a few patients, but we can still begin the discussion with the regulatory authorities with the nine patient data we have at hand. And the difference we're talking about is what I would call a... FDA-Related Feeds Issue rather than a design issue. The trial design, the randomized control design, the arm sizes, the size of the trial, the primary end-to-end. All that can be talked through and worked through. The only toggle is prophylactic steroids.

Station moves you see we will go with a fit with the prophylactic steroid or I mean design rather than a react to sell right. It's been enough data in enough programs to say that perplexed area, probably will better than reactive in general we have enough safety information on suggest that so our plan to put forth a prophylactic steroid approach.

We would like though to confirm that that works well testing a few patients, but we can still begin the discussion with the regulatory authorities with nine patient data and then the difference were talking about is what I would call a.

Drug administration related fee issue, rather than a design issue the trial design.

Controlled arm size, but trial the primary endpoint all that can be talked through work through the only toggle. It broke lactic steroids than we think thats a discussion we can have with the agency. So we will get an abrupt legs Jerry be done before we actually start but we can begin the process of regulatory conversation.

Emil D. Kakkis: And we think that's a discussion that we can have with the agency. So we will get a prophylactic steroid group done before we actually start. But we can begin the process of regulatory conversation for OTC. For GSD1A, we already are.

For OTI C.

Which is the one day we are.

Emil D. Kakkis: We're looking at the data, we'll put it out, and we'll have a call after the data come out so we can talk further about our next steps in the program. But in both cases, we're looking to head to the agency with the nine patient cohort information to make our call on the design and conduct of phase three. Great, thank you. I appreciate it.

We're looking at these data will put it out lobby call. After the data come out, but we could talk further about our next steps in that program, but in both cases were Acacia is ahead of the agency with the nine patients.

Cohort information to make or call and signed and conduct phase three.

Great. Thank you appreciate it.

Thank you. Our next question crossing Gena Wang of Barclays. Your line is open.

Yaron Benjamin Werber: Thank you. Our next question comes from Gena Wang of Barclays. Your line is open. Hi there, thanks for taking my questions. My name is David.

Hi, Thanks for taking my questions.

David I as my notes here, but yes. So it's so my first question is on slide 19, a team see any comment impact on the manufacturing specifically.

Gena Wang: Here's my notes. Here's for Gena. So anyway, so my first question is on COVID-19. Do you see any impact on manufacturing specifically? Yes, so far we have not seen a challenge for manufacturing. Our supply chain appears to be intact.

Yes, so far we've not seen.

Challenge for manufacturing our supply chain appeared to be intact. We also had substantial inventory on hand for all our products as we do or are rare disease programs, which gives us a lot of cushion, but this time, we're not seeing an act on manufacturing for the three products that are necessary.

Emil D. Kakkis: We also have substantial inventory on hand for all our products, as we do for our rare disease programs, which gives us a lot of cushion. But this time, we're not seeing an impact on manufacturing for the three products that are necessary to their commercial launch, and the third one would be the UX07 program. So, so far, all is good, and we're not having any issues with the supply chain. The next question is on GST-1A. So I was wondering, what are some initial thoughts on potential approval endpoints? So, for example, time-declared hyperglycemia, and also potential trial design for P3E. Well, I can start with the last part first. The trial design we've been discussing both for OTC and GSD-1A is a randomized control design and probably around 40 patients total. That's our expectation.

To their commercial in the third one would be the U.S. So seven program. So so far all is good and we're not having any any issues with supply chain.

<unk> mission is on.

Yes, Peter when a.

I was wondering what are some initial thoughts on potential approvable endpoint.

For example tend to grow advocate <unk> personal and those potential trial design for victory.

Well I can start with the last part first the trial design will be discussing gopro PC and just do you want to is a randomized controlled design and probably all around the 40 patient total that's our expectation we have not gotten agreement on that with DHS the basic design.

Gena Wang: We have not gotten agreement on that with EHB, but that's the basic design. The primary endpoint of GSE-1 is still to be discussed with the FDA, but we have several options ahead of us. Time-to-hypoglycemia was certainly one of the original ideas that we would do and certainly is one that we can show an effect on and is important. We're also seeing that the reduction in corn starch usage or requirement is another possibility

The primary endpoint of GST, one to still be discussed with the FDA. We have several options ahead of us time to hook with senior certainly one of the original ideas that we would do and certainly is one that we can show in effect on and it's important. We're also seeing that the reduction in corn starch usage or requirement is another possible it below.

He was continuous glucose monitoring opens the door to looking at more of a real world setting what is their hyperglycemia look like or how good is our glucose control.

Emil D. Kakkis: With continuous glucose monitoring, it opens up the door to looking at more of a real-world setting. The good part about GSD-1 is that glucose and its control are well understood by the agency and the medical community, and so we can work through that story, develop a plan, not just primary, but secondary endpoints will characterize what we believe is an improved glucose metabolism situation where patients can reduce their cornstarch dramatically, achieve good control of their glucose, and have other metabolic benefits. So we think there's a lot of ways to go, but whatever the endpoint will be, we'll talk a little more about it after we present our cohort 3 data. Thank you. Our next question comes from Maury Crawford of the Japanese Atlantic. Hi, thanks for taking my question. I have a GSD1A1 as well.

Part about GST, one is the glucose control well understood by the agency in the medical community and so we can work through that story Deval a plan not just primary secondary endpoints with cat characterize what we believe is an improved glucose metabolism situation, where patients can reduce their core search terms.

Medically achieved good control their glucose and have other metabolic benefits. So we think there's a lot of ways to go but.

Whatever the endpoint will be well talk a little more about it after we.

Present, our cohort three data.

Thank you. Our next question comes from Marty Krofft Cray parts of Jefferies. Your line is open.

Hi, Thanks for taking my questions.

Hi that GST want anyone is while just wondering if for the expansion cohort. If you can say generally modify time hyperglycemia challenge and reduce cornstarch of if that had an impact this cohort.

Maury Raycroft: Just wondering if for the expansion cohort, if you can say generally if the modified time to hypoglycemia challenge and reduced corn starch had an impact in this cohort. Well, we have done it, and we will see that data, but I don't want to discuss it. I think it's pretty natural.

Well, we have done it and you'll see that data, but I don't want to discuss on it I think it's pretty natural you to since you gave lift start they would get less glucose from it that's right pretty obvious.

Emil D. Kakkis: You'd assume if you gave them less starch, they would get less glucose from it. That's right, pretty obvious. We'll be presenting that data shortly, but as you might expect, the cornstarch quantity does impact how much glucose they get from it. Got it. Okay. And then for the continuous glucose monitoring, I'm wondering if you were able to get data from the initial cohorts that can be compared with the expansion cohorts, and should we expect some sort of dose-response comparison in the update? Well, we will be getting glucose monitoring on the earlier patients, but later in their course, we won't be able to look at before and after very well, so that will be one limitation, but we So, I think it will help confirm for us that the level of metabolic control glucose has improved in those patients. Whether we can interpret the dose exactly, I think the dose determination would require more than just one test. I think we have to look at it from multiple perspectives.

So we'll be presenting that data shortly.

But as you might expect corn starch quantity does impact how much glucose they get from it.

Got it Okay, and then for the continuous glucose monitoring I'm wondering if you were able to get data from the initial cohorts that could be compared with the expansion cohort and should we expect some sort of a dose response comparison.

Update.

Well, we will be putting getting.

Glucose monitoring on the earlier patients, but later in their core so we don't feel that look at before and after a very well.

So that will be one limitation, but we can look and see how are the what's their 20 for our fall looked like hyperglycemic events.

Hi, good is and the quality of their control the stable with it and consistent compared to what we know is common or the variably variability is common.

Based on corn starch treatment. So I think it'll help confirm for us that the level of metabolic control glucose has improved in those patients whether we can interpret the dose exactly I think the dose determination would require more than just one test I think we have to look at it from multiple parameters. There's only two stosur is that are in the.

Maury Raycroft: There are only two doses that are in the program at this point, 2E12 and 6E12. Our expectation is that we would assume that 6E12 is going to be a more potent dose based on the cohort data we have already.

Program at this point to a 12 Unsexy 12, our expectations that we would we would assume that 60 12, it's going to be a more dose cohort data we have already but.

Emil D. Kakkis: Between those two doses, I'm not sure CGM will provide the exact clarity we need. But I do think it will be one of the components that will help us confirm what we do going forward. Got it. Thank you. I'll hop back in the queue.

Between those two doses I'm not sure see Jim will provide the exact clarity I think some.

I do think will it would be one of the components will help us.

And from what we do go for going forward.

Got it thank you I'll hop back into queue.

Thank you. Our next question comes out of losses equal your line is open.

Maurice Thomas Raycroft: Thank you. Our next question comes from Adam Walsh of April. Your line is open. Hi, thanks for taking my question. This is Adam and John on behalf of Adam.

Hi, Thanks for taking my question. This is adamant zone on full Adam a quick question on Chris Beta for PCI Ole.

Maurice Thomas Raycroft: A quick question on CRISPR for TIO, which I hope you will get FDA approval very soon. First, are tumors that cause TIO typically benign? Is Chris Vita mainly targeting those patients whose tumor cannot be surgically removed? And how many TIO patients are in this category, based on your estimates? Sure, thank you. In general, the vast majority of tumors are benign. There have been a few patients that had malignant tumors who do make FGS-23 and do have the bone problems associated with them, but the majority of the patients we're talking about have benign, small little tumors, mesenchymal source tumors that are making a little bit of FGS-23.

Which I hope you've got the FDA approval very soon.

First of tumor or not close jaco typically benign.

It's Chris with a mainly targeting those patients whose tumor cannot be surgically removed.

And how many tio patients you this category based on your estimates.

Thanks.

Sure. Thank you so in general the vast majority of the tumors are benign there have been a few patients that had malignant tumors. We do make FGF 23, and do have the bone problems associated but the majority of base are talking about have benign small little tumors mesenchymal sourced tumors that are making a little.

But it just 23.

We don't have good precise numbers on T. O the United States, but we believe it's in the round the out of the 2000 and around half of them have non respectable tumors that we'd be more likely candidates for treatment.

Emil D. Kakkis: We don't have good, precise numbers on T.O. in the United States, but we believe it's in the round of 1,000 to 2,000, and around half of them have non-resectable tumors that would be more likely candidates for treatment. Non-resectable means that you have to have found the tumor, which sometimes is hard to do. And secondly, it has to be a tumor in a place that you can remove it without causing other harm.

Nonres sector was first means you have to sound the tumor sometimes it's hard to do and secondly, it has to be a tumor in a place that is.

You can you remove without causing other home and so there's a lot of ways. You can end up situation were krissy that might be better option, whether immediately or in the long run.

Emil D. Kakkis: And so there's a lot of ways you can end up in a situation where a CRIS VITA might be a better option, whether immediately or in the long run. So I would assume it's about half of the total population at this point in time. So relative to XLH, it's much smaller, but the population with TIO is very severe in many cases and very devastating. And so there is a high urgency to treat it, which is why we did a program because we were getting compassionate use requests for access. Great, thank you. Thank you. Our next question comes from Laura Chico Webber. Your line is open. Good afternoon. Thanks for taking the questions. I guess maybe a couple on the Angelman program with GTX-102.

So I would assume it's about half of the total population for at this point in time, so relative to escalate, it's much smaller but population T. O is very severe many cases and very devastating and there is a high urgency to treat which is why we did a program to be we're getting compassionate use request for access.

Great. Thank you.

Thank you.

Next question comes from large Chico Wedbush Your line is open.

Good afternoon, thanks for taking the questions I guess, maybe a couple on the interim my program with Gtx, one or two I.

Laura Kathryn Chico: I know you've dosed the first two patients already, and just wondering if you could remind us, are there certain regions of the brain that are going to be more important to achieve distribution? I believe in the murine model we saw UBE3A expression pretty consistent across the entirety of the brain, but just interested in your thoughts there. And then, related to that, what proportion of Angelman patients are currently on anti-epileptic drugs? Thank you. So with regard to the first part, I don't know that going into a very deep neuro-anatomy discussion probably on the conference call is going to work, but we can do a follow up on that. What I would say to you is the following. What we know from the data they have done in mung is that the oligonucleotide, the ASO, is getting to a wide variety of brain regions and inducing transcription, you know, of the UB3A gene.

I know you dose the first two patients already and just.

Wondering if you could remind us are there certain regions of the brain that are going to be more important to achieve a distribution I believe in a marine model. We saw you be three expression pretty consistent across the entirety of the brain.

But just interested in your thoughts there and then related to that what proportion of Angelman patients are currently on anti epileptic drugs.

Thank you so with regard to the first part I don't know that going into a very deep neural anatomy discussion problem. Commscope go work, we can do a follow up on that what I would state use following what we know from the data they have done in monkeys.

The the all going into the tide is though is getting to a wide variety of brain regions and inducing transcription.

Of the you'd be three gene. So we know the treatment effect that growth is broad throughout the brain regions and so we feel pretty comfortable whatever reasons needs to get treated that there is reasonable distribution and uptake of the itself for the action. We can go deeper separately, but I'd rather not go until the.

Camille L. Bedrosian: So we know the treatment effect is broad throughout brain regions, and so we feel pretty comfortable that whatever regions need to get treated, there is a reasonable distribution and uptake of the ASO for its action. And we can go deeper separately, but I would rather not go into all this. The second part you asked is the percent who have seizures. I don't know if Camille happens to have that knowledge. I know it's a significant fraction, but it's certainly not all of them.

The second part you asked as a percent with seizures I don't know if Camille happens to have that knowledge and my I know, it's never been fraction, but it's certainly not all of them I don't remember a number off my head is the substantial fraction.

Camille L. Bedrosian: I don't remember a number off the top of my head, but it's a substantial fraction. Camille, any thoughts? Yeah. Yeah, thank you, Emil. Thank you for the question. Exact proportion, I don't know either, but what I do know is that most, if not all, patients do have an abnormal EEG, which is quite pathognomonic of the disorder.

Meal any thoughts yep.

Thank you ammo. Thank you for the question.

Exact proportion I don't know either but what I do know is that most if not all patients do have an abnormal E G.

Which is quite passing demonic of the disorder.

Thanks, very much follow up on that number yep.

Camille L. Bedrosian: Thank you very much, follow up on that number. Thank you. Our next question comes from Yigal Nochomovitz of Citi. Your line is open. Hi, this is Samantha Andreagal.

Yeah.

Thank you.

Our next question comes when you get out notional motive of Citi. Your line is open.

Hi, This is my math on vehicles famous for taking my question.

Yigal Dov Nochomovitz: Thanks very much for taking the question. On the Diagee manufacturing deal, it's very interesting, and particularly since it's non-exclusive. I wonder, can you first speak to specifically what makes the manufacturing platform unique in terms of scalability versus others in the space?

On the dashi manufacturing.

You, saying and Jason if not it plus as one that to you first she just specifically what makes manufacturing platform unique in terms of scalability versus others and space and also can we expect you to be interested in doing in Malaysia other companies in the future.

Emil D. Kakkis: Also, can we expect you to be interested in doing similar deals with other companies in the future? Well, I can answer the second part first, which is, yes, we're interested in doing other deals. We wouldn't do many because we do have to do tech transfer and support to partner with HE, but we could certainly do another deal. The basic thing that's important that they're buying into is the fundamental reality that it's very hard to do triple transfection on a very large scale. We can get to 200, 400, 500 liters. Getting to 1,000, 2,000 gets to be quite difficult to do reliably and to mix and create, besides the fact that the plasmid dose is not scaling. It is essentially linear scaling, which means costs don't continue to go up.

Well I can enter answer the second part which is yes. We are we're interested in doing other deals you wouldn't get many because we do have to do tech transfer. It supports the partner they too, but we could do certainly another deal.

For another two the basic thing this important if they're buying into the fundamental realities as very hard to do triple trend section in very large scale.

Yes, 200, 400 500 leader.

2000, 2000 gets to be quite difficult to do reliably and to mix and create besides the fact that the plasma dose is not scaling is essentially linear scaling cheese cost will continue to go up so the Sheila system is a reliable 2000 leader culture system and because fuel cells are very.

Emil D. Kakkis: So the HeLa system is a reliable 2,000 liter culture system, and because HeLa cells are very strong growers and they're grown in suspension, we can basically take a clonal cell line which has in it the information to guide the production of the AAV and grow it to 2,000 liters in a fully healthy, fast-growing culture, and then just add adenovirus, small amounts of it, to very efficiently infect And this turns the whole tank into an AAV production machine. The cells stop growing and start making AAV.

Strong growers and they've grown suspension, we can basically take a closer look fell on which has ended the the information to guide the production of Avi.

Grow into 2000 leader fully healthy fast growing culture.

And then just at the end of our small amounts that are very efficiently affect the entire culture. Just like you would if you're doing vaccine manufacturing and this create trends the whole tank into an AB production machine. So stop growing start making a the so the idea is it can grow the cells to large scale in a very healthy situation and then effects the more.

Emil D. Kakkis: So the idea is that you can grow the cells at a large scale in a very healthy situation and then infect them more efficiently. It's just going to be way more efficient than doing triple transfection at a large scale. And we're talking about 2,000 liter scale, which is the largest in terms of scale that's out there. That's because that's the disposable reactor size. We believe that the Helix system could potentially be used for 10,000 liters to create the right stable pump.

Additionally, it's just the way more efficient than doing triple transaction at large scale now we're talking about 2000 leader scale, which is the largest maintenance it's out there that's because that's the disposable reactor size.

We believe that he'll assist could potentially use for 10000 leader you create the right stable clone.

Emil D. Kakkis: And so you could even go larger, but it wouldn't be a disposable bioreactor at that scale. That is just not going to be true for triple transfection. And the truth is that being able to do that without the material cost of plastic and other reagents to simply grow these cells up on a large scale and use a very inexpensive antivirus inducer to induce AV production. It's just going to be a substantially more efficient, more effective way to make AAV. The quality of the AAV that you make in that system, which is very similar to the natural biological situation, right, with an adenohelper and the adenovirus as the source of functions, provides a higher fill ratio of the product that's made and a better quality product out of the reaction to begin with. So you get larger scale, less cough material, and a larger reaction, you know, and a more effective quality of the

And so you could even go larger but it wouldn't be a disposable fire actors that scale that it's just not going to be true for triple transfection and the truth is that being able to do that without the trail cost with plastic.

The reagents, we simply grow these cells up in large scale and use of very inexpensive end of our do search to induce Avi production is just going to be a substantially more efficient more effective way to make a b quality vectren made in that system, which is very similar to the natural biological situation right.

No helper.

With the AD Novartis is the source of functions.

Provides a higher fill ratios the product that's made a better quality product.

Actually begin once you get larger scale west cost material in a larger reaction.

Our effective quality of the product. So there's a those are some of the factors I think that people are seeing as we get more and more commercially the programs, especially ones needing higher dose.

Emil D. Kakkis: So those are some of the factors I think that people are seeing as we get more and more commercial AV programs, especially ones needing higher doses. Quality and scale of manufacturing are something we have. The world's getting smaller. Thank you very much for all of that detail. And just on the tech transfer, can you speak to what the typical timeline for completing that is? Well, it's over an 18 month period expected, although there's a period of continuous support for a five year period, but most of the tech transfer is expected over about an 18 month period, and basically, their people come to us; we'll go to Japan.

Scaling quantity and coffee factoring from start to become a key factor because I don't think the world to take every gene therapy, two or $3 million. So at some point throughout the things about all these diseases and how we're going to do this and I think.

Quality and scale of a manufacturing is something we haven't I think.

The world is going to need.

Thank you very much for all of that detail and just on the tech transfer he speaks to what the typical timeline for completing that is.

Well, it's over an 18 month period expected, although there's a period of continuous support for a five year period, but most the tech transfer expected over about an 18 month period and bits through their people come to US we'll go to Japan and of course works were all moving around the ideas to teach them how to do all of it and to help.

Them create their own PCL lines and do their own manufacturing in Japan and have a plant that they're going to convert to that you.

Yigal Dov Nochomovitz: Okay, great. Thank you. And then just one more, if I could.

Okay. Thank you and then just somewhere if I could.

Emil D. Kakkis: With the prophylactic steroid cohort currently paused before you can dose those patients you've lined up, assuming this headwind continues a bit further into the second half, how many weeks on therapy will you need before you're confident that you can advance into phase three using the prophylactic steroid dosing method? Well, we'll be advancing the phase three plan in parallel with doing this. So this will allow it to kind of, be able to before we do the first patient in, have significant data. Obviously, we think 12 weeks is enough to say whether patients are doing well. Well, but it's more like 24 weeks to know how well they're re-adjusted when they've got enough steroids. But, so that's the kind of time frame, but what I'm saying to you is we can keep working on the plan for phase two up until the first patient comes in.

Which he I'd like to start cohort apparently pause before you can josias patients have lined up.

I'm, assuming this headwind kitchenaid is it fair there.

The second half how many weeks on therapy, we need before you're confident that you can advance into the phase three I using the perfect extent right dosing Mahesh.

Well, what we will be advancing the phase three plan in parallel with doing that so this will allow us to kind of.

Be able to before we do first patient.

We will have significant data, obviously, we think 12 weeks Dave's enough to say weather stations are doing.

Well there is more like 24 weeks to know how well there regency's and they've gotten upstairs, but plus a kind of timeframe, but wouldn't change you as we can keep working the plan for phase two.

Up until first station in what I said, our plan would be to go with prophylactic steroids is our proposal and just getting that confirmations, there's nothing unusual happen to be able to reassure.

Emil D. Kakkis: What I said was our plan would be to go with prophylactic steroids as our proposal and just get that confirmation. There's nothing unusual happening to be able to reassure FDA that this is in our cells, that there's no issue with doing it that way. As long as the first 12 weeks go well, we know it's safe, we know what the potency looks like in that time frame, and we'll collect data probably through 24 weeks to get a sense of whether we're getting better potency.

Is there that this is a and ourselves that theres no issue with doing that way as long as a first 12 weeks go well we know it's safe we know what the potency looks like in that timeframe and we will collect did it probably from 24 weeks to get them, whether we're getting better potency.

Yigal Dov Nochomovitz: Thank you very much for taking our questions. Thank you. Our next question comes from Corey Casimo of J.P. Morgan. Afternoon, this is Turner on for Corey.

At least.

Hey, I think famous for taking my question.

Oh.

Thank you. Our next question causal Cory Kasimov of JP Morgan Your line is up.

Afternoon. This is turnaround for Corey I'm just on the Angelman study I'm curious how frequently are assessing functional endpoints and what's your confidence to be able to demonstrated improvement in 128 day timeframe and just to that point with the physicians, you're working with or interacted with what do they deem as meaningful improvements from base.

Corey Casimo: Just on the Angelman study, I'm curious how frequently you're assessing functional endpoints. And you know, how confident are you that you'll be able to demonstrate an improvement in the 128 day timeframe? And just to that point, with the physicians you're working with or have interacted with, what do they deem as meaningful improvements from baseline on those functional endpoints? Thanks. Very good. That's a very long, detailed question. Well, the Injuryman program should be up on ClinDotribe.gov, but I'll have Camille answer your question on the frequency, in general, certainly at a high level.

On August functional endpoints. Thanks.

Great. Good that's a very long detailed question would well, we'll Benjamin program should be up on claim to transact, but I'll have to meal into your question on the frequency in general it certainly at a high level I don't know plants are all the changes in every endpoint at this point, but can you. Please go ahead.

Right sure. Thank you Im all thank you for the question also yes patients are.

Camille L. Bedrosian: I don't know if I'll answer all the changes in every endpoint at this point, but Camille, go ahead. Right, sure. Thank you, Emil. Thank you for the question also. Yes, patients are evaluated for developmental and debilitating abnormalities along the way, so there are a number of assessments. In terms of what is meaningful for the patients, as you can imagine, sleep dysfunction, balance abnormalities, difficulty walking that leads to falling, seizures, as discussed previously, and most profoundly, the inability to speak, and varying degrees of not being able to communicate as well.

Evaluated every call.

To every month as well and there are a large number of assessments across a number of domains because these patients experience.

Developmental and debilitating abnormalities, along the way so there are a number of assessment.

In terms of what is meaningful for the patients as you can imagine sleep dysfunction.

They balance abnormalities difficulty walking that leads to falling seizures as was discussed previously and most profoundly the inability to speak.

And varying degrees of not being able to communicate as well so right now we're learning in this first in human study and as we go and we'll be able to described and discuss.

Camille L. Bedrosian: So right now, we're learning in this first human study, and as we go, we'll be able to describe and discuss not only this study but also what we're seeing in terms of what is meaningful. I would add, as we get further along in the program, closer to actually having data, we'll provide more depth to the endpoints and expectations of what's meaningful. All the endpoints do have meaningful thresholds for what we mean, but how precise that is when you're talking about a multi-system disorder like this.

Oh, the up not only in this study, but also what we're seeing in terms of why this meaningful.

I would add as we get further along in the program closer to actually having data will provide more depth to the end points and expectations of what meaningful all the endpoints do have meaningful threshold through what the but how precise that is when you're talking about it multisystem disorder like doses. So is complex.

Camille L. Bedrosian: It's complex, so we need to still learn, as Camille has noted, and we look forward to providing more detail about the analysis and the interpretation of that data as we get closer to it. Thank you. Thank you. Our next question comes from Liisa Bayko of JMC Securities. Hi, this is John Walden on behalf of Liisa.

So we do still earn its communal has noted.

We look forward brought in more detail about the analysis in the interpretation that data as we get closer to it. Thank you.

Thank you. Our next question comes from Liisa Bayko JMP Securities. Your line is open.

Hi, This is John Waldron on for Lisa Thanks for taking the question.

Liisa Ann Bayko: Thanks for taking the question. Just on the 007 launch, you mentioned that there are about 160 metabolic centers that you're looking at. Can you discuss kind of your launch strategy and how you're tiering those potentially or what doctors you're targeting at first and how that might change over time? Sure, I'll start and let Erik finish.

Just on the Oh seven launch a you mentioned that there are about 160, but a book centers that you're you're looking at can you discuss kind of your launch strategy and how you're hearing those potentially or what doctors you're targeting.

At first and how that might change overtime.

Sure I'll start and let them Eric finished the.

Emil D. Kakkis: See, we're very familiar with the 160 metabolic centers. We're already seeing them in MPS. We're seeing them for our OTC program, GSD-1A program, GSD-3 program. I've seen them before for Kuvan, for Alterozyme, for Naglozyme. So it's a group that we've seen a lot of different products that we know very well. We know these centers because we've been involved in a number of clinical trials with them. So certainly they're always key attenuators, but there'll be a segment among those.

We're very familiar with 160 metabolic there's the early seeing them for MPS, we're seeing them for OTI see program GST. One a program GC three program I've seen them for Ku band filters sign for next time. So it's a group that we've seen a lot of tripled product you know very well we know these centers because we have involved in the number.

Clinical trials with them. The certainly there are always Houston leaders, but theres they'll be a segment of one of those and but maybe a less Eric talked about the strategy are easy to.

Erik Harris: But maybe I'll let Erik talk about the strategy we're using to launch O7 in the Manage Your Metabolic Center. Thanks, Emil. As he stated, the majority of the patients are at those 160 metabolic centers across the country where we already have a strong presence and a strong relationship, and then there's also high awareness centers around 007. So our primary focus at launch is going to be transitioning those trial patients on to commercial therapy, and we expect those trialers to also describe O07 for some of the other patients that didn't enter the trial. So we think we'll be able to leverage our current infrastructure with a relatively small and efficient team to support the launch somewhere between 5 to 10. Thank you. Our next question comes from Vincent Channa Bernstein. Your line is open. Hi, this is Brian on for Finstant.

Launch.

But the manageable center.

Yes, thanks animal.

Say that the majority of the patients are at those a 160 metabolic centers across the country.

And when we already have a strong presence and strong relationships.

And then there's also high awareness.

At those centers around.

Seven.

Our primary focus and launch is going to be.

Transitioning those trial patients onto commercial therapy, and we expect.

Those are those travelers to also.

Prescribed.

Seven for somebody other patients that none of the trial. So we think we'll be able to leverage our current infrastructure.

But the small relatively small and efficient team to support the launch somewhere between five to 10 incremental hires.

Very good thing Claire.

Thank you.

Our next question comes from Vincent Chen of Bernstein. Your line is open.

Hi, Brian offer phones, and all I guess long on the Wilson's disease program. I was wondering if you can provide any color just on how you're thinking about what patients you might be going after it just my understanding that.

Vincent Channa: I guess one on the Wilson's disease program. I was wondering if you could provide any color just on how you're thinking about what patients you might be going after. It's just my understanding that, largely speaking, Wilson's disease is pretty well controlled by chelation therapy. And this is also a very large indication.

Largely speaking welcome disease is pretty well controlled by accumulation therapy and this is also very large indication. So I guess I'm just wondering how you're thinking about a target patient population there.

Emil D. Kakkis: So I guess I'm just wondering how you're thinking about a target patient population there. Yes, so thank you. There will be some Wilson clinical data at the SBCC on the program. If you're interested in wealth, you can look for that data.

Yes. Thank you.

There will be some.

Wilson.

It is TCT on the program. There if you said, we'll speak for that data coming out.

Emil D. Kakkis: It's coming out soon. The clinical strategy right now is to look at patients that clearly have significant, they're off stably on their drugs, they clearly have significant symptoms. It's very, right now in the early stage, we want patients who are not acutely ill because we need to establish safety. First, patients being studied are relatively stable, and then the patient population will expand later.

The clinical strategy right now to look at patient the clearly have the skin aeropostale. Other drugs. We clearly have symptom is very right now the early stage, we want patients were not acutely ill because we need to establish the safety.

Designed the study will outpatient.

First being studied that a relatively stable and then patient population will expand later.

Emil D. Kakkis: We haven't really put out those details yet because we haven't discussed them with regulatory authorities. But clearly, when you look at the 50,000 plus Wilson patients, there are some that may be doing quite well on their chelators and may not need additional help. But the focus for gene therapy is on a substantial fraction that are.

We haven't really put out those details yet you haven't discussed them with regulatory authorities, but clearly when you look at the 50000 plus Wilson patients. There are some that maybe doing quite well in their key leaders and may not need additional hall.

Focus for gene therapies on a substantial fraction that are still having progression of disease or it's still having symptom. Despite accumulation. So I think there's a significant fracture patients and their and ultimately this the program will focus on those.

Emil D. Kakkis: [inaudible] Thank you. I'm showing no further questions at this time. I'm going to turn the call back over to Daniel Keatley for any closing remarks. Thank you. And this concludes our call for today. A replay will be available soon. And if you have additional questions, please contact us by phone or at ir at ultragenyx.com.

Great. Thanks.

Thank you I'm showing no further questions at this time I turn the call back every Daniel Keatley for any closing remarks.

Thank you and this concludes our call for today, a replay will be available in and you have additional question. Please contact us I phone or an IR at Ultragenyx dotcom. Thank you for joining us.

Danielle Keatley: Thank you for joining us. Thank you. Ladies and gentlemen, this concludes today's conference. Thank you for participating. You may all disconnect.

Thank you ladies and gentlemen, this concludes today's conference thanks for participating email disconnect.

[music].