Q3 2023 Ultragenyx Pharmaceutical Inc Earnings Call

Speaker 1: Good afternoon and welcome to the ultragenics third quarter, 2023 financial results conference call. At this time, all participants are in a listen only mode. At the end of the prepared remarks, you will have an opportunity to ask questions during the Q&A portion of the call. It is now my pleasure to turn the call over to Joshua Higa, Vice President of Investor Relations.

Good afternoon, and welcome to the Ultra genetics third quarter 2023 financial results Conference call. At this time all participants are in a listen only mode. At the end of the prepared remarks, you will have an opportunity to ask questions. During the Q&A portion of the call. It is now my pleasure to.

Turn the call over to Joshua <unk>, Vice President of Investor Relations.

Speaker 2: Thank you. We've issued a press release detailing our financial results, which you can find on our website at oprogenics.com.

Thank you.

Issued a press release detailing our financial results, which you can find on our website at <unk> Dot com.

Speaker 2: Joining me on this call are Amel Cactus, Chief Executive Officer and President, Eric Harris, Chief Commercial Officer, Howard Horn, Chief Financial Officer, Eric Crombez, Chief Medical Officer, Aaron Olson, Senior Vice President of Corporate Strategy and Finance, and Ted Heizanga Chief Accountant.

Joining me on this call our aim of chocolate Chief Executive Officer, and President Eric Harris, Chief Commercial Officer, Howard Horn, Chief Financial Officer, Eric Crumbles, Chief Medical Officer.

Eric Olson senior Vice President of corporate strategy and apps.

Zynga Chief Accounting officer.

Speaker 2: I'd like to remind everyone that during today's call, we're making forward-looking statements. These statements are subject to certain risks and uncertainties and our actual results made different materially. Please refer to the risk factors discussed in our latest SEC filings. I'll now turn the call over to Hamel. Thank you.

I'd like to remind everyone that during today's call, we'll be making forward looking statements. These statements are subject to certain risks and uncertainties and our actual results may differ materially. Please refer to the risk factors discussed in our latest SEC filings I'll now turn the call over to cable.

Thanks, Josh and good afternoon, everyone.

Speaker 3: Before we get started, I'd like to welcome our new CFO , Howard Horan, to the call.

Before we get started I'd like to welcome our new CFO Howard warn to the call.

Speaker 3: He was hit the ground running as an understatement. He already has an ulti-genic, analyst day, and a financing under his belt. We're happy to have him on board as we prepare for a catalyst for his 2000-24.

Today, he has hit the ground running as an understatement. He already has an old genetics analyst day end of financing under his belt.

We're happy to have him on board as we prepare for a catalyst rich 2024.

Speaker 3: It's great to see many of you at our analyst day a few weeks ago. We hope that the new data shared has event along with the positive clinical impressions of the investigators on two of our programs show you why we have confidence in our lead therapeutic candidates in their potential to transform the builtating disease with limited or no treatment options.

It was great to see many of you at our analyst day, if he'd be weeks ago. We we hope that the new data shared has he been along with the positive critical impressions of the investigators on two of our programs.

So you why we have confidence in our lead therapeutic candidates and their potential to transform debilitating diseases with limited or no treatment options.

Speaker 3: We kicked off the day by sharing new data from the orbit study for cetuzumab in osteogenesis in perfecta. It has been prevented a few days earlier at ASPMR, the Sberic Society for Bone Mineral Research 2023 at the annual meeting.

We kicked off the day by sharing new data from the orbit study personnel treat the mab and osteogenesis imperfecta.

And that's been prevented a few days earlier than a S. P M or the spirits side for bone mineral research 2023 annual meeting.

Speaker 3: Interim data from the Phase II portion of the study demonstrated that the TREASIMAD significantly reduced the analyzed fracture rate by 67%. After at least six months of treatment, it continued to demonstrate ongoing substantial increases in lumbar spine bone marrow density reaching 19% in just six months in the younger patient.

Interim data from the phase two portion of the study demonstrated that <unk> significantly reduced the analyzed fracturing by 67%.

After at least six months of treatment.

Continue to demonstrate ongoing substantial increases in lumbar spine bone mineral density, reaching 19% just six months in the younger patients.

Speaker 3: We also provided an update on our GTX 102 program in Angelman syndrome.

We also provide an update on our Gtx 102 program in age when syndrome.

Speaker 3: The data we covered was longer-term extension data from the dose escalation cohorts in the Phase 1-2 study, and it showed that treatment with GTX12 resulted in clinically meaningful improvements across multiple domains through both the loading and maintenance.

The daily recovered with longer term extension data from the dose escalation cohorts in the phase one study.

And it showed the treat with Gtx one tube resulted in clinically meaningful improvements across multiple domains.

Felt the loading and maintenance phase of treatment.

Speaker 3: The improvements we saw in Bayley and the Angement Severity Assessment, formerly known as the CGI-S Severity Scale, were also supported by objective changes in EEG and comparisons to natural history.

The improvement we saw in Bailey and the agent severity festivals, formerly known as a C. G. I guess ask severity scale were also supported by objective changes in EDG and comparisons to natural history.

Speaker 3: We also looked at the emerging first-ever development changes from three of the original US patients. When these patients stopped receiving G-Chick one and two, they lost these first-ever development and gains. But we're able to gain these skills once the third tree moves, new dose and regimen.

We also looked at the emerging first ever development changes from three of the original U S patients.

When these patients stopped receiving gtx wanted to the lawsuits first effort about fill up mental games.

But we're able to gain these skills once they start treating new dosing regimen.

Speaker 3: Other patients also found many first-ever development gains, which gives us confidence in the potential transformative factor for this neurodevelopmental disease.

Other patients all with so many first ever development gains, which gives us confidence in the potential transformative effect that neuro developmental disease.

Speaker 3: These first hours are very important to the families and give clinical meaningful to the changes we are seeing in the quantitative effects.

These first areas are very important in the family can get clinical meaningful to the changes we're seeing in the quantitative assessments.

Speaker 3: The third program we highlighted was our UX701 AAV gene therapy for Wilson disease.

The third program, we highlighted with our UX 701, AAV gene therapy for Wilson disease.

Speaker 3: We provide data on the five patients in the first lowest dose cohort. At 5E12 GC per kilo, four of five patients showed improvements in coppographic and had begun tapering off-canada care with key layers and or zinc therapy.

We provide data on five patients in the first lowest dose cohort.

At five <unk> GC per kilo for the five patients showed improvement in copper trafficking.

And had begun tapering off standard of care with <unk> therapy.

Speaker 3: This includes two of the earlier treated patients who are now completely off standard of care and doing well.

Difficult to the earlier treated patients who are now completely off standard of care and doing well.

Speaker 3: Air Chrom is will provide more TTO updates on these programs later in the call. But as clear, we have three large value programs all generating data that meaningfully de-risk the probabilities of their success.

Eric <unk>, who will provide more detailed updates on these programs later in the call, but it's clear we have three large value programs. All January data that meaningfully derisk the probabilities of their success.

Speaker 3: Now I'll turn the call over to Eric Harris for writing an update on our commercial efforts for the first quarter.

Now I'll turn the call over to Erik Harris to provide an update on our commercial efforts for the first quarter.

Speaker 2: Thank you, Amel, and good afternoon, everyone. After five years of successfully commercializing for speedering North America, this responsibility was transitioned to Giao Karen on April 27, 2023.

Thank you Emil and good afternoon, everyone. After five years of successfully commercializing proceed here in North America. This responsibility was transitioned to <unk> on April 27.

2023.

Speaker 2: Small OFU-DNX-FIL team and patient support services team was kept to help the KIAO here in FILT team find and start dying. Dying those patients while ensuring a smooth hand.

As part of the transition a small orthogenic spill team and patient support services team was capped to help the kyowa Kirin <unk> find in stock guidance diagnose patients, while ensuring a smooth handoff.

Speaker 2: With the combined field efforts, the demand for stock forms throughout this year has remained strong and has greater than what we saw during the same period last year.

With the combined field efforts the demand for stock forms throughout this year has remained strong.

And is greater than what we saw during the same period last year.

Speaker 4: In recent months, the majority of the stock forms have come from adult patients.

In recent months the majority of the stock loans have come from adult patients.

Speaker 4: which further supports our strategy of expanding the search and community positions.

Which further supports our strategy of expanding the search as a community physicians to find these patients.

Speaker 4: The two teams are working hard to ensure patient and physician continuity while continuing to identify new subscribers and patients.

The teams are working hard to ensure patient and physician continuity, while continuing to identify new prescribers.

And patients.

Speaker 4: Shifting to Latin America, shifting to Perfeta in Latin America, as of Q3 2023, there are over 460 patients on Riembers therapy, which includes approximately 50 new patients who began from commercial therapy.

Shifting to Latin America shifting to proceed in Latin America as of Q3 2023.

Our over 460 patients on reimbursed therapy, which includes approximately 50, new patients who began commercial therapy in this quarter.

Speaker 4: This year alone, we have converted approximately 150 new patients to the commercial growth.

This year alone we have converted approximately 150, new patients to the commercial drug in this region.

Speaker 4: The Latin America team has continued to build its rather moment.

Latin America team has continued to build solid momentum.

Speaker 4: Further strengthen by the recent reimbursement approval for pediatric patients.

Further strengthened by the recent reimbursement approval for pediatric patients from the largest public payer in Mexico.

Speaker 4: from the largest public payer in Mexico called IMF-SF.

Speaker 4: Caspita is approved in six countries in Latin America, including Argentina, Brazil, Chile, Colombia, Mexico, and Peru.

SaaS.

Chris Peter is approved in six countries in Latin America, including Argentina, Brazil <unk>.

Selling.

Colombia, Mexico and Peru.

Speaker 4: for zero continues to be the largest market in Latin America. And we continue to see growing demand.

Brazil continues to be the largest market in Latin America, and we continue to see growing demand.

Speaker 4: while the uneven ordering parents in Brazil address and quarter to quarter variability to underline demand remains strong.

In this country.

While the uneven ordering patterns in Brazil will drive some quarter to quarter variability.

Speaker 4: Today, we are reaffirming the Procedede Guidance we issued at the beginning of the year. The range of $325 to $340 million includes all regions and all forms of Procedede Revenue.

You're lying demand remained strong.

Today, we are reaffirming the procedure guidance, we issued at the beginning of the year the range of $325 million to $340 million includes all regions and all forms of pursuit of revenue.

Speaker 4: more specifically, it includes perfeiter product revenue from Latin America.

More specifically it includes procedure product revenue from Latin America.

Speaker 4: and Turkey and the cash and non-cash royalties from North America in Europe . And the collaboration property of revenue prior to the transition.

And Turkey, and the cash and noncash royalties from North America, and Europe, and the collaboration with profit share revenue prior to the transition.

Speaker 4: For the guilty in North America, the demand for star forms remains strong.

For the <unk> in North America.

And for Star forms remains strong in the U S. We have added nearly 19 start forms and converted over 70 patients to reimburse throughout this year we.

Speaker 4: In the US, we have added nearly 19 star forms and converted over 70 patients to reimburse throughout this year.

Speaker 4: We continue to expand the number of treaters of visual beauty in the US, adding 30 new prescribers this year, including some healthcare professionals in the service from your own muscular meds.

We continued to expand the number of treaters of video in the U S. Adding 30, new prescribers this year, including some health care professionals and the centers for neuromuscular medicine.

Speaker 4: In Canada, we continue to make progress following a positive opinion from Canada.

In Canada, we continued to make progress following a positive opinion from Canada, completing pan CPA pricing negotiations.

Speaker 4: completing PAN CPA pricing negotiations and signing listing of rings.

Signing listing agreements.

Speaker 4: Outside of the U.S., there continues to be growing demand for the COVID. In Latin America, our commercial teams are continuing to identify more patients, and we expect demand will continue to steadily increase over time.

Outside of the U S. There continues to be growing demand for video.

In Latin America, our commercial teams are continuing to identify more patients and we expect demand will continue to steadily increase over time.

Speaker 4: across Europe , we continue to deepen the awareness for LCF and LD and key stakeholders, and address the high-end medical need through main patient and early access program.

Across Europe, we continued to deepen the awareness for LC <unk> key stakeholders.

And address the high unmet medical need through main patient and early access programs.

Speaker 4: Requests are coming from across all major European markets, as well as Greece, Israel, and the Middle East.

Requests are coming from across all major European markets, as well as Greece, Israel and the Middle East.

Speaker 4: Today, we are reaffirming our 2023 global digital revenue guidance range of $65 to $75 million. The range we announced at the beginning of the year.

Today, we are reaffirming our 2023 global <unk> revenue guidance range of $65 million to $75 million range, we announced at the beginning of the year.

Speaker 4: Lastly, on a pizza, we continue to make progress in major markets in Europe and the Middle East.

Lastly on a feedback we continue to make progress in major markets in Europe, and the Middle East.

Speaker 4: Kisa has now proved in Germany where we have started to convert patients to commercial drugs.

As Keith has now approved in Germany, where we are starting to convert patients to commercial drug.

Speaker 4: In many other countries, the demand is steadily growing as patients gain access to FESA through various early access programs.

In many other countries the demand is steadily growing as patients gain access to a fever.

Through various early access programs.

Speaker 4: In Canada, we received marketing approval from health Canada for adults and pediatric patients aged five years in order with HLFA.

In Canada, we received marketing approval from health, Canada for adult and pediatric patients aged five years and older.

FH.

Speaker 4: We also continue to make steady progress in Japan, where we have meeting scheduled later this year with the Ministry of Health, Labor, and Welfare to discuss pricing and reimbursement. We also continue to make steady progress in Japan, where we have meeting scheduled later this year with the Ministry of Health, Labor, and Welfare to discuss pricing and reimbursement.

We also continued to make steady progress in Japan, where we have meetings scheduled later this year with the Ministry of health Labor and welfare to discuss pricing and reimbursement.

Across all regions.

Speaker 4: received overwhelmingly positive feedback. We have keys there from PLLs and patients.

We have received overwhelmingly positive feedback for FTE there from Kols at patients and they have continued to highlight the significant unmet need for this disease and the importance of this potent new treatments.

Speaker 4: They have continued to highlight the significant unmet need for this disease and the importance of this potent new treat.

Speaker 4: and continue to respond to many urgent requests for early access, and our teams will continue their efforts to bring this product to people living with AQFH as quickly as possible.

We continue to respond to many urgent requests for early access and our teams will continue their efforts to bring this product to people living with AQR phage as quickly as possible.

Speaker 4: In closing, we are reaffirming our 2023 total revenue guidance range, issued at the beginning of the year, a $425 to $460 million.

In closing.

We are reaffirming our 2023 total revenue guidance range issued at the beginning of the year.

$125 million to $450 million.

Speaker 4: With that, I'll turn the call to Howard to share more details on the financial results for the quarter.

With that I'll turn the call to Howard to share more details on the financial results for the quarter.

Speaker 2: Thanks Eric. It's great to join the team for today's call. Before we get into the numbers, I'd like to thank Ted, Aaron, and their teams for all of their contributions over the last year.

Thanks, Eric it's great to join the team for today's call before we get into the numbers I'd like to thank Ted Erin and their teams for all their contributions over the last year.

Speaker 4: They implemented a number of important initiatives around financial discipline, which have contributed to the strength of our current financial position.

We implemented a number of important initiatives around financial discipline, which have contributed to the strength of our current financial position.

Speaker 2: I will briefly summarize the financial results that were included in the press release we issued earlier today.

I will briefly summarize the financial results that were included in the press release, we issued earlier today.

Speaker 2: Starting with revenue, our total revenue for the third quarter was 98 million.

Starting with revenue our total revenue for the third quarter was $98 million.

Speaker 2: Chris Vita revenue for the third quarter was $75 million, which included $50 million from North America, $19 million in product sales, primarily from Latin America, and approximately $6 million in European royalty and other product revenue.

Chris Vita revenue for the third quarter was 75 million, which included $50 million from North America.

$19 million in product sales, primarily from Latin America, and approximately $6 million in European royalty and other product revenue.

Speaker 2: As we have previously disclosed, the third quarter US Chris Vita revenue was negatively impacted by a one-time decrease in channel inventory related to key occurrence change from ultra-genics labeled product to key o'cure-enabled product as part of the transition of North America commercialization responsibility.

As we have previously disclosed the third quarter U S. Chris Vito revenue was negatively impacted by a onetime decrease in channel inventory related to <unk> change from ultra genex labeled product to kyowa Kirin labeled product as part of the transition of North America commercialization responsibilities.

Speaker 2: Again, this is a one-time change, and we expect Chris Vita channel inventories to increase to more normal levels at the end of the year.

Again. This is a one time change and we expect Chris Vida channel inventories to increase to more normal levels at the end of the year.

Speaker 2: The Jolvi revenue for the third quarter was $17 million, with North American demand driving 25% growth versus third quarter 2022.

The jewelry revenue for the third quarter was $17 million with North American demand driving 25% growth versus third quarter 2022.

Speaker 2: Shifting to expenses, our total operating expenses for the third quarter were $243 million, which included R&D expenses of $157 million, SG&A expenses of $75 million, and cost of sales of $11 million.

Shifting to expenses, our total operating expenses for the third quarter were $243 million, which included R&D expenses of $157 million.

SG&A expenses of $75 million and cost of sales of $11 million.

Speaker 2: Operating expenses for the quarter included non-cash stock-based compensation of $35 million.

Operating expenses for the quarter included noncash stock based compensation of $35 million.

Speaker 2: For the third quarter, NetLoss was $160 million or $2.23 per share.

For the third quarter net loss was $160 million or $2 23 per share.

Speaker 2: As of September 30, 2023, we had 524 million in cash, cash equivalents, and marketable security.

As of September 32023, we had $524 million in cash cash equivalents and marketable securities.

Speaker 2: After the end of the quarter, we raised an additional 326 million from an underwritten public offering of common stock and pre-funded warrants.

After the end of the quarter, we raised an additional $326 million from an underwritten public offering of common stock and pre funded warrants.

Speaker 2: Through the third quarter, net cash used in operations was $391 million.

Through the third quarter net cash used in operations was $391 million we.

Speaker 2: We expect fourth quarter net cash used in operations to be around $35 million, driven by anticipated strong fourth quarter revenues and factoring in expected changes in working capital.

We expect fourth quarter net cash used in operations to be around $35 million driven by anticipated strong fourth quarter revenues and factoring in expected changes in working capital.

Speaker 2: As a result, we now expect full-year net cash used in operations to be around $425 million.

As a result, we now expect full year net cash used in operations to be around $425 million.

Speaker 2: The team has worked hard over this past year to ensure we are in a strong financial position, and we will continue to build on these efforts going forward.

The team has worked hard over this past year to ensure we are in a strong financial position and we will continue to build on these efforts going forward.

Speaker 2: Now I'll turn the call to our CMO, Eric Krombez, who will provide an update on our key clinical programs.

Now I will turn the call to our CFO, Eric <unk>, who will provide an update on our key clinical programs.

Thank you Howard and good afternoon, everyone and momentum the key clinical updates we shared at analyst day, and I'll provide just a bit more detail on our priority programs.

Speaker 4: Emil mentioned the key clinical updates we shared at animal state, and I'll provide just a bit more detail on our priority.

Speaker 5: starting with UX143 or citruthamab for the potential treatment of osteogenesis in perpetuity.

Starting with the UX 143, or so truth I mab for the potential treatment of osteogenesis imperfecta.

Speaker 5: The data we presented as analysts supports our view that this is a disorder of inadequate bone production as much as it is about defects in collagen.

The data we presented at the Analyst day supports our view that thats okay.

Disorder of inadequate palm production as much as it is about defects oncology.

Speaker 5: Across the 24 patients enrolled in the phase 2 portion of the ORBIT study, we saw an improvement in bone mineral density z-score of 0.85.

Cross the 24 patients enrolled in the phase II portion of the orbit study we saw an improvement in bone mineral density of these score of $85 six months importantly, a subset of five to 12 year old saw nearly a 20% increase in bone mineral density with a Z score change of one one.

Speaker 5: Importantly, the subset of 5 to 12-year-olds saw nearly a 20% increase in bone mineral density with a z-score change of 1.1%.

Speaker 5: These improvements in bone mineral density across the 24 patients treated in the orbit phase suit translated to a 67% reduction and the annualized fracture rate following treatment with Chousamab for at least.

Nine.

These improvements in bone mineral density across the 24 patients treated in the orbit phase two translated to a 67% reduction and the annualized fracture rate following treatment with <unk> for at least six months.

Speaker 5: 20 of the 24 patients did not experience any new fractures in the six months following treatment with.

20 of the 24 patients did not experience any new fractures in the six months following treatment with the truth in that.

Speaker 5: For the four who did have a radiographically confirmed fracture, many of them occurred early on in treatment or had a traumatic precipitated

For the four who did have a radiographically confirmed fracture many of them occurred early on in treatment or had a dramatic precipitating event.

Speaker 5: The data is all the more compelling, because many of the patients in this study were previously treated with bisphosphonates over the two years prior to dosing with citrus.

The data is all the more compelling because many of the patients in that study were previously treated with <unk> over the two years prior to dosing.

With such as amount. During this time these patients continued to see a high annualized fracture rate with many fractures are occurring but very minimal activity. These types of fractures are referred to as for agility fractures and examples include fractures are occurring during sleep or when transferring out of a chair.

Speaker 5: During this time, these patients continue to see a high annualized fracture rate with many fractures occurring.

Speaker 5: These types of fractures are referred to as fragility fractures, and examples include fractures occurring during sleep or when transferring out of a chair.

Speaker 5: What we heard from two principal investigators who joined us at Animalist Day is that they are not seeing fragility fractures in these studies patients treated with atruzumab, and that many of these kids are now feeling strong enough to engage in more physical activities with fragility.

What we heard from two principal investigators who joined US at Analyst day is that they are not seeing fragility fractures. In these studies patients treated with <unk> and that many of these kids are now feeling strong enough to engage in more physical activities with friends and family.

Speaker 5: Next, turning to GTX 102 for the potential treatment of Angelman Syndrome, where we showed clinically meaningful improvements across multiple domains for the patients in the loading and maintenance phases of the dose escalation goalers for through seven.

Next turning to Gtx 102 for the potential treatment of Angelman syndrome, where we showed clinically meaningful improvements across multiple domains for the patients and the loading and maintenance phases of the dose escalation cohorts four through seven.

Speaker 5: With the long-term extension data, we showed improvements compared to natural history data and supportive EEG data, providing further evidence that the changes we are seeing are meaningful and improving over time.

With a long term extension data, we showed improvements compared to natural history data in support of EEG data, providing further evidence that the changes we are seeing are meaningful and improving over time.

Speaker 5: We also share data from three of the original US patients who stopped and restarted.

We also shared data from three of the original U S patients, who stopped and restarted treatment.

Speaker 5: These patients gained, lost, and regained a number of skills, including following complex directions.

These patients gained loss and regained a number of skills, including following complex directions.

Speaker 5: communicating needs and wants and improved behavior.

<unk> needs and wants and improved behaviour in sleep.

Speaker 5: These changes show the importance of GTX-102 to enable continued development in these patients with the hope that they will continue to learn and develop new skills.

These changes show the importance of Gtx 102 to enabled continued development in these patients with the hope that they will continue to learn and develop new skills.

Speaker 5: Dr. Elizabeth Berry-Kravis, who is a principal investigator for the

Dr. Elizabeth Barrett Kravitz, who is a principal investigator for the study took us through a few video examples of what these developmental improvements translate to for her patients and their caregivers Dr. Barry <unk> has been working with Angelman patients in our clinic for decades and noted that it can take years for these patients to learn right.

Speaker 5: Check us through a few video examples of what these developmental improvements translate to for for patients and their care.

Speaker 5: Dr. Barry Kravitz has been working with Angelman patients in our clinic for decades and noted that it can take years for these patients to learn a single new skill. So the fact that these patients are learning multiple things in such a short amount of time is

Single new scale for the fact that these patients are buying multiple things in such a short amount of time is remarkable.

Speaker 5: Enrollment in the dose expansion cohorts, cohorts, a 3 continues to go well, and we anticipate sharing data from at least 20 patients who have been on therapy for at least 6 months in the 1st, half of.

Enrollment in the dose expansion cohorts cohorts as <unk>.

<unk> to go well and we anticipate sharing data from at least 20 patients who have been on therapy for at least six months in the first half of 2024.

Speaker 5: Lastly, UX701 for the potential treatment of Wilson disease, which is a disorder of copper track.

Lastly, <unk> 701 for the potential treatment of Wilson disease, which is a disorder of copper trafficking as.

Speaker 5: As Emil mentioned, we are seeing a response in 4 of the 5 patients treated in the first dosing cohort with patients 2 and 3 completely discontinuing their chelators and

As Emil mentioned, we are seeing a response and four of the five patients treated in the first dosing cohort with patients two and three completely just continuing their key later as Android thing.

Speaker 5: At analyst a, we said that cohort to receiving a dose of 1, 813 has been fully.

At Analyst day, we said that cohort two receiving any dose of 113 has been fully enrolled.

Speaker 5: DSMB is scheduled to meet soon to review the available data, which will enable initiation of dosing in the third and final cohort in state.

SMB is scheduled to meet soon to review the available data, which will enable initiation of dosing in the third and final cohort in stage one.

Speaker 5: If five patients for this last dose escalation court have been identified and need enrollment eligibility, we expect dosing in this court.

Five patients for those last dose escalation cohort have been identified and meet enrollment eligibility.

We expect dosing and Thats core to complete around the end of the year.

Speaker 5: The improvement in copoviral markers and ability to reduce current standard of care are promising signs of the establishment of normal trafficking of copper in these patients, and we look forward to sharing additional progress with this important gene therapy program.

The improvement in capital Biomarkers and the ability to reduce current standard of care are promising signs of the establishment of normal trafficking of copper in these patients and we look forward to sharing additional progress, but thats important gene therapy program.

Speaker 5: I'll now turn the call back to Emil to close with the key upcoming milestones and provide some closure.

I'll now turn the call back to ammo to close with a key upcoming milestones and provide some closing remarks.

Speaker 3: Thank you, Eric. I'll summarize the key upcoming clinical catalyst and before we open up to Q&A.

Thank you Eric I'll summarize the key upcoming clinical catalysts and before we open up to Q&A.

Speaker 3: Starting with UX143, so I just imperfect that enrollment, both of the phase three stages going well with strong support for the medical community following both of our data releases this year. We're enrolling at 50 sites around the world and they're tired and complete enrollment in the first quarter next year. We also expect to provide another longer term data updates from the phase two portion of the study next year. Next, GTA Co.

Starting with <unk> III for Us just imperfect.

Enrollment in both the phase III studies is going well with strong support for the medical community. Following both of our data releases. This year, we're rolling it 50 sites around the world are tired and complete enrollment in the first quarter next year.

We also expect to provide another longer term data update from the phase II portion of the study next year.

Next gtx onto an Angelman syndrome.

Speaker 3: Based on the patients who are currently enrolled in Dose, we are on track to provide an update on the expansion course in the middle of the first half of 2024.

Just on the patients who are currently enrolled in dose we are on track to provide an update on the expansion of course, the middle of the first half of 2024.

Speaker 3: And as we have said, we'll include at least 20 patients of data. We've been on through.

And we said as we have said to include at least 20 pages of the data.

We've been Ontario for at least six months.

Speaker 3: We'll include long-term efficacy data on early enrollees and a safety update on the total exposed population.

And include longer term efficacy data on early enrollees and a safety update on the total exposed population.

Speaker 3: Closing with our gene therapy program, GTX411 for GST1A, DOS, the last patient pillow study earlier this year. We're now in the 48-week window and expect to unblind and share this phase three date in the first half of 2024.

Closing with our gene therapy program <unk> hundred one for GSD, one a dose the last patient in pivotal study earlier. This year. We are now in the 48 week window and expect to underline is share the phase III data in the first half of 2024.

Speaker 3: US-111 for SAMHSA Lipo Syndrome. We are continuing to see meaningful clinical responses in these patients, and we're working with the FDA around biomarker data to help support an accelerated.

<unk> hundred 11 for Sanfilippo syndrome.

We're continuing to see Nathan clinical responses in these patients and we're working with the FDA around biomarker data to help support an accelerated.

Approval filing.

Speaker 3: GTX 301 for OTCs and rolling patients in the Bay 3. And we expect the last patient to be dealt in the first half of 2024.

<unk> 301 for OTC is enrolling patients in the phase III and we expect the last patient to be dosed in the first half of 2024.

Speaker 3: UX701 for Wilts disease should have all patients dose in stage one this year. And we expect to provide safety and efficacy data on all of these patients in the first half of 2024.

UX seven one for well to these should have all patients dose in stage one this year.

And we expect to provide safety and efficacy data on all of these patients in the first half of 2024.

Speaker 3: We've worked hard over this past year to ensure we are in a strong financial position heading into 2024 and beyond. We continue to see growing demand for our commercial products and completed financing that gives us the ability to advance our large value program through meaningful inflection points. We've been employing more aggressive financial discipline, including realigning our headcount, restructuring in places, and doing the work we need to make sure we're putting the people and capital where we have the ability to generate the most value.

We've worked hard over this past year to ensure we are in a strong financial position heading into 2024 and beyond we continue to see growing demand for our commercial products and completed a financing that gives us the ability to advance our large value program through meaningful inflection points.

We've been employing more aggressive financial discipline, including realigning our head count restructuring in places and doing the work we need to make sure we're putting the people and capital where we have the ability to generate the most value.

Speaker 3: Alternatives come a long way since our humble beginnings. As I said analyst, they expect to have around eight to 12 approvals in our first 15 years post IPO. And these are in extremely debilitating disease with urgent need for treatment options. I think that really demonstrates the responsibility we feel to lead the future of rare disease matters.

Ultra has come a long way since our humble beginnings as I said.

At Analyst day, we expect to have around eight to 12 approvals in our first 15 years post IPO and these are in extremely debilitating disease with urgent need for treatment options.

I think that really demonstrates responsibly, we feel to lead the future of rare disease medicine.

Speaker 3: With that, let's move on to your questions, operator. Please provide the Q&A instruct.

With that let's move on to your questions. Operator, please provide the Q&A instructions.

Speaker 1: Thank you. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. One moment for a question.

Thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, one moment for questions.

Speaker 1: Our first question comes from Monopom Ramo with JP Morgan. You may proceed.

Our first question comes from <unk> Rama with Jpmorgan you May proceed.

Speaker 5: Hey guys, thanks so much for taking the question and welcome, Howard, hope you're well man. So I got a quick broader question here, which

Hey, guys. Thanks, so much for taking my question.

Welcome Howard Hope, you're well ma'am.

So I got a quick broader question here, which is what are you monitoring here for the <unk> DMD gene therapy regulatory review process that could maybe potentially retreat your broader gene therapy efforts and pipeline and then on one of your gene therapy program, specifically 401 and GSD one.

Speaker 5: What are you monitoring here for the Surrepted DMD gene therapy regulatory review process that could maybe potentially re-pute your broader gene therapy efforts and pipeline? And then on one of your gene therapy programs, specifically 401 and GSD1, we heard a little bit about that program at R&D Day, but maybe you could help us to find a wind scenario for that program when you flip the card and maybe help us understand the market opportunity a little. Thank you guys so much. Yeah, always thought about it.

We heard a little bit about that program at R&D day, but maybe you can help us define a win scenario for that program. When you flip the card and maybe help us understand the market opportunity here a little thank you guys. So much.

Very good thank you for the question so.

Speaker 3: As everyone knows, the surreptive Phase III and blinding showed the primary endpoint of NSAA, but hit throwing to other endpoints. I think it shows that the drug is working. I think the NSA is a terrible endpoint. And frankly, I've said people we would never want to work with that endpoint because it's just a clinician score. So it's not so surprising. I think the drug shows us working. And it'll be up to surreptive to manage that forward. I think...

As everyone knows the sewer up to phase III in blinding showed with the primary endpoint of NSA, a but hit.

<unk> strong two other endpoints.

I think it shows that the drug is working I think the LSA as a terrible endpoint and frankly I've said people, we would never want to work with that endpoint because it's just a clinician score so it's.

It's not so surprising I think the drug shows is working.

It will be up to throw out to manage that forward I think.

Speaker 3: What I was saying in the broader context for our own program is that the ability to deliver Microsoft is having an important clinical benefit in these patients. It's still a first step in the path for improved care for these patients, but we think, I think in general it says that these Microsoft and Gene Therapy programs can work and we're still encouraging, still pressing our own program ahead in development.aky replacement issues, and it ultimately pertains to the personnel lending fee for health.

What I would say in the broader context for our own program is that the ability to to deliver micro structurally is having an important clinical benefit in these patients is still a first step in our path toward improved care for these patients, but we think I think in general It says that these micro dystrophin gene therapy program can work and we're still encouraged.

Still pressing our own program ahead in development.

With regard to 401 <unk>.

Speaker 3: The program, you know, we think there's something around 68,000 patients, you know, and about a fourth of that would be US patients.

The program.

Think there's something around six to 8000 patients and about a fourth of that would be U S patients.

Speaker 3: The majority of these patients, like 80 plus percent of the patients are no, have no or very, eventually no enzyme. What that means is 80 percent of the patients are severe. That means 80 percent of the patients are risk of dying if they miss a dose of cornstarch. These are the patients that have...

The majority of these patients like 80 plus percent of the patients are no have no or very essentially no enzyme what that means is 80% of the patients are severe that means 80% of patients are at risk of dying if they miss a dose of cornstarch. These are the patients that have essentially had done to their had taken cornstarch every day to drive refer adopt.

Speaker 3: since you had done that they had taken cornstarch every day. Driver for adoption is a piece of mind of knowing I'm not gonna die if I forget to take my cornstarch. And we think that's a big driver. We believe it's one of the reasons why the space we trial and roll so quickly.

Is the is the peace of mind, knowing I'm not going to die if I forget to take required starts and we think thats a big driver. We believe it's one of the reasons why the phase II trial enrolled so quickly people really wanted to get out of this treadmill that theyre on with corn starch and sugar control.

Speaker 3: People really wanted to get out of this treadmill that they're on with cornstarch and sugar control.

Speaker 3: And the fear of every night being a potential, you know, risking death is something went wrong. Or if they go and exercise, they could collapse and be hypodysemic.

And the fear of every night being a potential risking death, if something went wrong or if they don't exercise they could collapse in the hypoglycemic.

Speaker 3: So we think there's a big demand and drive. Of course, cornstarch is not commercially...

So we think there's a big demand and drive of course cornstarch is not commercially costly, but I do think the peace of mind and stability at people, who can live a life instead of one full of fear I think it is big and we have high hopes that the adoption of the treatment will be.

Speaker 3: costly, but I do think the peace of mind and the ability of people who can live a life instead of one and full of fear I think it's big and we have high hopes and that the adoption of the treatment will be Will be more aggressive and bris just it was in the enrollment of the trial which enrolled everywhere in fact

We'll be more aggressive in Nebraska, yes. It was in the enrollment of the trial, which enrolled everywhere. In fact, we had a lot of people upset when we closed enrollment that couldnt get in the trial. So we think the demand is going to be there and while it's not a huge program. It's we think 8000 patients since a substantial one and we think that there will be.

Speaker 3: We had a lot of people upset when we closed enrollment that couldn't get in the trial. So we think the demand is gonna be there. And while it's not a huge program, it's...

Speaker 3: We think 8,000 patients is a substantial one and we think that there will be...

Speaker 3: early adoption for that program and I do think that the clinical demand and need is important. I think we've seen it for that program. So I'm pretty encouraged so far.

Early adoption for that program and I do think that the clinical demand and need is important and I think we've seen it for that program. So I'm pretty encouraged so far.

Okay.

Thanks, so much.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from DeGona with people you may proceed.

Our next question comes from Dae Gon Ha with Stifel. You May proceed.

Speaker 6: Great, good afternoon. Thanks for taking our questions. Two, maybe on GTX 102 and the Satruzumab, just wanted to clarify on Satruzumab, able to do stay enrollment completion in 1Q24. Is that for both orbit as well as cosmic?

Great. Good afternoon, thanks for taking our questions to maybe on Gtx 102 in <unk> just wanted to clarify on <unk> did you say enrollment completion and <unk> 24 is that for both orbit as well as cosmic and are you, placing any protocol restrictions on strenuous activity I mean, that's encouraging there.

Speaker 6: And are you placing any protocol restrictions on stringent with activity? I mean, it's encouraging there being more active and fearless, but in terms of endpoints, I wonder if that could kind of create a confounder. For GTX 102, update in first half 24, what kind of data should we be expecting? You had ASA, MDRI, as well as Bayley for, but if you could frame that for us, it would be great. Thanks so much.

Being more active in <unk>, but in terms of endpoints I wonder if that could kind of create a confound or for Gtx 102 update in first half 'twenty for what kind of data should we be expecting you had <unk> as well as bailey for but if you could frame that for us that would be great. Thanks, so much.

Speaker 3: Very good. Thank you. So for the cheese map, we're talking about both orbit and cosmic in terms of finishing enrollment. I think we're likely, but the main one we're talking about is orbit, which is the main driver. I believe both of them should get done in that timeframe.

Very good data on thank you so.

Choose mab, we're talking about both orbit and cosmetic in terms of finishing enrollment I think we're likely but the main one we're talking about his orbit, which is the main driver, but I believe both of them should get done in that timeframe.

Speaker 3: And in terms of this controlled exercise or the hazard risk of someone feeling better and exercising, well, that's already what's happening in safety. People were a lot more active than what was...

And in terms of this controlled exercise or the hazard risks, if someone feeling better and exercising well that's already what's happening in phase two people were a lot more active than what was.

Speaker 3: Actually on the plus side is that they were active in law. And we're we're falling into that fracture necessarily. So while there is some risk that they might be doing more, there was one person who played volleyball and they they hadn't been playing. We're actually overall feeling that the the pattern of having falls and fractures seems to be better. And so our net effect overall is we think even with increased activity, there'll be a reduction for actors.

Actually on the plus side is that they were active in a lot of them are we're following it didn't have fractures necessarily so while there is some risk that they might be doing more there was one person who played volleyball.

It hadn't been playing.

Overall, feeling that the pattern of having falls and fractures seems to be better and so our net effect overall, we think even with increased activity there'll be a reduction in fractures.

Speaker 3: which is really the best thing possible that it's a kidney active and to have a reduction in the fraction while being active. So we're not so worried about the, let's say the noise of having more fracture risk at this point. It looks like you still see the effect well, even if there is some risk there.

Which is really the best thing possible that if the kids are going to be active and to have reduction of fractures, while being active so we're not so worried about the.

Let's say the noise of having more fracture risk at this point it looks like you'll still see the effect well, even if there is some risk there.

Speaker 3: Now with regard to GTIX 102, I expect the data to be many of the same things you've seen, which is the Bayley's, which we'll compare, of course, in that for history data. For the main three endpoints we talked about, and there were others three that we looked at for the ESA. There are other endpoints. We didn't describe all the endpoints we had. We had said at the meeting that things like the Vineland.

Now with regard to Gtx one too.

The day to be many of the same things that <unk> seen which is the baileys.

Which will compare of course, the natural history data for the main three end points, we talked about and there were other three that we looked at for the USA. There are other endpoints. We describe all the endpoints. We had we had said at the meeting that things like the Vineland.

Speaker 3: and others had a very similar pattern of response to those. So, but I would look for data to be very similar to the package of data that you saw.

And others had a very similar pattern of response to those so but I would look for data that would be very similar to the package of data that you saw.

Speaker 3: that we'd probably doing something very similar to what you saw before in terms of comparison in natural history. And the essay, we'll try to include enough information to interpret the quantitative changes and the meanfulness of those changes, which I think is one of the debates.

That would probably be doing something very similar to what you saw before in terms of comparison and natural history and.

PSA we will try to include enough information to interpret the quantitative changes and the meaningfulness of those changes, which I think is one of the debates.

Speaker 3: And we're certainly going to look at emerging skills as well in those patients as best we can. So those are the things I think you'd expect to see. It should be 20 patients, six month data. There will be probably 10 patients that have longer data out the 254 and more than 30 patients worth of data of any type. So it should be a pretty robust set of data. So I'm looking forward to that.

And we're certainly going to look at emerging skills as well in those patients.

As best we can so those are the things that I think you'd expect to see it should be 20 patient six month data there will be <unk>.

10 patients that have longer data out the $2 54 in.

More than 30 patients worth of data of any type so should be a pretty robust set of data. So I'm looking forward to that.

Thanks next question.

Thank you.

A moment for our next question.

Speaker 1: Our next question goes from Jeffrey Hum, with Morgan Stanley , he may proceed.

Our next question comes from Jeffrey <unk> with Morgan Stanley You May proceed.

Speaker 7: Hi, this is Michael Riada, I'm from Jeff Hung. Thank you for taking our question. For the truth, how do you think regulators will view the clinical benefit for younger patients who are still developing versus adults who are more or less finished growing? Is there any appreciation for the ability to prevent factors and complications to eventually bone deformations? Thanks so much.

Hi, This is Michael on for Jeff Holmes. Thank you for taking our question.

<unk>, how do you think regulators will view the clinical benefit for younger patients who are still developing versus adults who are more or less finished growing is there any appreciation for the ability to prevent fractures and complications to eventually like bone deformation. Thanks, so much.

Speaker 3: Well, I think you're hitting on a really important thing. Let's talk about what the FDA asked or they wanted to have.

Well I think you're hitting on a really important thing, let's talk about what the FDA asked for or they wanted to have the major clinical fractures, excluding fingers toes and skull as the endpoint because they feel those with most clinically meaningful.

Speaker 3: The major clinical fracture is excluding fingers, toes and skull.

Speaker 3: as the end point because I feel those are most crankly meaningful.

Speaker 3: However, whatever they think is one thing, they're dealing with fractures from osteoporosis. The truth is what you talked about is really important that is the vertebral fractures and other types of fractures that result in deformation of the bone are actually things that drive very poor outcomes. So our trial would have pediatriced and also has a very young group of patients.

However, whatever they think is one thing they're dealing in fractures from osteoporosis. The truth is what you talked about is really important that as the vertebral fractures and other types of Fracs. The result in deformation of the bone are actually things that drive very poor outcome. So our trial, which will have pediatrics and also had some very young group.

Speaker 3: We'll look at not just clinical fractures, but also vertebral fractures and other fractures, which we think will benefit.

Patients will look at not just clinical practice, but also vertebral factors and other factors, which we think will benefit. So I think we will be able to show the clinical fractures and hit the fda's required endpoint, but we hope to be able to expand that to talk about other aspects of the disease, particularly in the very young patients and the cosmic study.

Speaker 3: So I think we'll be able to show the clinical fractures and hit the FDA's required endpoint, but we hope to be able to expand that to talk about other aspects of the disease.

Speaker 3: particularly in the very young patients in the cosmic study and to be able to show how support for their verbal problems.

And to be able to show how support for their vertical Toms.

Speaker 4: you know would not result in the kind of degeneration degradation that leaves them all to be wheelchair bound as you know five or six year old

Would not result in the kind of degeneration degradation that leaves them all to be wheelchair bound is five or six year olds.

Speaker 4: I think that would be an amazing result. We're gonna see what we do. But based on the very substantial lumbar spine, bone marrow density improvement, I'm 20% of some of the young kids, we kind of expect this spine to be strong and to change the future of not deforming like they've had in the past.

I think that would be an amazing result, we're going to see what we do but based on the very substantial lumbar spine bone mineral density improvement of 20% in some of the young kids, we kind of expect this line to be strong and to change the future of not to forming like they they've had in the past.

Speaker 4: So I would say we can prove the FDA get our approval, but the broader acceptance of the treatment and its reimbursement will be supported by the rest of the body of data, which we are including in our plan. That's really, really helpful. Thank you so much, Sharers.

So I would say, we can prove the FDA and get our approval, but the broader acceptance of achievement and it's reimbursable will be supported by the rest of the body of data, which we are including in our plan.

That's really really helpful. Thank you so much for your response.

Thank you one moment for questions.

Speaker 1: Our next question comes from you gal, not come over it's with city you may proceed.

Our next question comes from Yigal <unk> with Citi. You May proceed.

Speaker 8: I think this is Carly on Furia Goll. Thanks for taking our questions.

Hi, Tim This is Carly on sorry, Yigal, thanks for taking our questions. We had one commercial question.

Speaker 8: We had one commercial question. It's like you're expecting a pretty significant re-acceleration in revenues in the fourth quarter in order to meet the guidance range. Now you mentioned an inventory impact to proceed during the third quarter, but can you talk a little bit more about your assumptions driving that acceleration in revenue that you're expecting?

It looks like you're expecting a pretty significant acceleration in revenues in the fourth quarter in order to meet the guidance range.

You mentioned <unk>.

Inventory impact of Christina during the third quarter, but can you talk a little bit more about your assumptions driving that acceleration in revenue that you're expecting thank you.

Speaker 4: Sure, let me hand that over to Eric. The fourth core has a lot of differences in how things perform. There's always a lot of lumpiness as well, but Eric, if you want to deal with what you think, how we're going to go to the fourth quarter, yeah, I think if you look at previous years, we've always had a strong fourth quarter. So it's a typical seasonality, which will also this year, will entail some inventory rebuilding following the NDC swap out.

Sure, let me I'll hand that over to Eric.

The fourth quarter as a lot of differences.

How things perform and Theres always a lot of lumpiness as well, but Eric if you want to deal with what you think how revenue is going to go in the fourth quarter. I think if you look at previous years, we've always had a strong fourth quarter. So it's typical seasonality.

This will also this year will entail some some inventory rebuilding.

Following the MDC swap out.

Speaker 4: And as I stated earlier, the man remains very strong. In fact, our demand in dog forms is higher than it was.

And then as I stated in earlier demand remains very strong in fact, our demand.

Start forms.

It is higher than it was at this point last year.

Speaker 4: Boo ming confidence that uh will see us on

So we remain confident that.

Obviously, a strong fourth quarter, Yeah, I think if you go back and look Youll see every fourth quarter.

Speaker 2: Yeah, I think if you go back and look, you'll see every four quarters has been a quarter. So we're on track. We think pretty good about where we are on the business.

There has been a quarter or so.

We're on track, we think pretty good about where we are in the business.

Speaker 8: Okay, great, Festival. And then maybe just one follow up related to the Wilson program. Can you have how you're thinking about the size of the addressable population for a gene therapy approach in Wilson's and maybe what you're hearing from K-Wells about the proportion of patients not well managed on key leaders and on the more severe end of the disease spectrum that could be addressable? Thanks.

Okay, Great. That's helpful. And then maybe just one follow up related to the Wilson program.

Just how youre thinking about the size of the addressable population for <unk> gene.

Gene therapy approach in Boston, and maybe what you're hearing from Kols.

That's a question of patience.

Not well managed on keloid, Arizona.

March year end.

We expect that that could be addressed to Bob. Thank you.

Speaker 3: I think that the Wilson market potential is an important question. The 50, 50,000 patients probably more because it's underdiagnosed in my view.

Yes, I think the.

The Wilson market potential is an important question.

The 50 to 60000 patients probably more because it's under diagnosed in my view.

Speaker 3: And you can look at it as maybe the 20th of the patient that aren't well managed is the core indication, but I think the...

And you can look at it is maybe the 20% of patients are not well managed the core indication, but I think with the drop out of the Alexia on AZ calculator as competitor and showing that just chelation is not good enough to make patients better the doors open to the idea that <unk>.

Speaker 3: drop out of the Alexion AZ keyulator as competitor and showing that just the relation is not good enough to make patients better. The doors open to the idea that improving copper distribution could make patients feel better, do better than you can get just with a key later, which means it might not be just a 20 plus percent that have

Proving copper distribution could make patients feel better do better than you can get just with a key later, which means it might not be just the.

20, plus percent that have problems with their key later as it could mean more of the majority of the patients with Wilson, we're encouraged that the patients are getting off their there.

Speaker 2: problems with their key later, so it could mean them more of the majority of the patients will often. We're encouraging that the patients are getting off their...

There.

Speaker 3: Yeah, the keylators, but I think we're also really encouraged that the coprolose abuse seems to be improving even as a lower dose as in that patient seems to be feeling really good. My hope is if you restore coprolose to be used in that the effect of coprolose deficiency, which is occurring in a Wilson disease.

Yes, the key later, but.

We're also really encouraged that the copper distributions improving unit, the lower doses and that patients seem to be feeling really good.

My Hope is if you restore copper distribution that the effect of copper deficiency, which is occurring in Wilson disease.

Speaker 3: overlayed on top of copper toxicity is a real factor. And if we can make people feel a lot better and perform better, I actually think there's a potential to be an education that becomes a majority of patients.

Laid on top of copper toxicity is a real factor and if we can make people feel a lot better and perform better I actually think there is a potential it has to be <unk>.

Any indication of that becomes the majority of patients because of our ability to manufacture with identical platform in our own plan keeps the costs really low. It also means we can manage the pricing in a more intelligent way that would enable a larger fraction of these patients to get put on therapy and actually build a bigger business model out of.

Speaker 2: Because our ability to manufacture with the pinnacle platform in our own plant keeps the cost really low, it also means we can manage the pricing in a more intelligent way that would enable a larger fraction of these patients to get put on therapy and actually build a bigger business model out of it.

Speaker 3: than one based on a 3 million a price point, which I think makes it more challenging. So we look at the opportunity here as potentially larger than the initial views if we can make patients feel better, do better. And I think there's a real chance for that with the Wilson gene therapy.

It.

Then one based on a $3 million of parish and kind of price point, which I think makes it more challenging. So we look at the opportunity here is potentially larger than the initial views. If if we can make patients feel better do better and I think there's a real chance for that with the Wilson gene therapy.

Great very helpful. Thank you.

Thank you one moment for your next question.

Speaker 1: Our next question comes from Tadina Madh with Thank You America, you may-

Our next question comes from Praveen <unk> with Bank of America You May proceed.

Speaker 9: Hi, thank you so much for taking my question. email like maybe just wanted to clarify one point, and then sorry if it was already asked before, but when you talked to the FDA about downsizing the OY.

Hi, Thank you so much for taking my question.

Maybe just wanted to clarify one point.

And then sorry, if it was already asked before but when you talk to the FDA about downsizing DIY phase III trial.

Speaker 10: trial. You were supposed to get specific feedback on that. Just wanted to hear your thoughts on what FDA's view on that particular request was or if you're

We're supposed to get specific feedback on that just wanted to hear your thoughts on what FDA view on that particular.

The request was or if you're still waiting to hear back. Thanks.

Speaker 3: Yes, we have really discussed the details are going through that, but

Yes, we havent really discuss the details of going through that but.

Speaker 3: The plan on the Phase III with the addition of the interim assessments, we think it won't be a problem.

The plan on the phase III with the vision of the interim assessments, we think won't be a problem.

Speaker 3: But we haven't really disclosed any ongoing discussion with them, but we're comfortable with the ability to get the interim set. And besides the studies really up to us, you know, in terms of safety, the exact trial size is well above 100 patients before the adequate size. So we'll come up with a plan with them, but I'm not concerned about our ability to get that accepted. Okay. Thank you.

We haven't really disclosed the ongoing discussion with them, but we're comfortable with the ability to get the interim set and the size of the study is really up to us in terms of safety.

<unk> trial sizes, well above a 100 patients in Florida, the adequate size. So we will come up with a plan with them, but I am not concerned about our ability to get that accepted.

Okay. Thank you.

Thank you one moment for questions.

Speaker 1: All right, this question comes from Chris and Clusco with kind of a Cheryl, you may proceed.

Our next question comes from Chris <unk> with <unk>.

Sheryl you May proceed.

Speaker 11: Hi everyone, thanks for choosing the question. Can you provide any more color or thoughts around the timing of the intermonialities of the O.I. study?

Everyone. Thanks for taking them.

Question can you provide any more color or thoughts around the timing of the interim analysis of the study.

Speaker 12: Yes, the way the interns will be done, we won't be disclosing when they're happening. We've said there we'd expect a first one to happen this coming year.

Yes.

The interim will be done.

We won't be disclosing when theyre happening we've said there we would expect our first one happened in this coming year.

Speaker 12: We want to make sure that patients had at least a certain amount of time of treatment before an interim would be done. And the original plan for the program was to operate off of the fracture information, how many fractures it worked, and to the event driven timing. So the precise timing is we haven't disclosed. It depends a little on fracture numbers, et cetera.

We want to make sure that patients had at least a certain amount of time of treatment before our interim would be done in the original plan for the program is to operate off of the fracture information how many fractions of our essentially event driven timing. So the precise timing is we haven't disclosed it depends a little on fracture numbers et cetera.

Speaker 12: But we said that one error will occur next year, but we won't disclose exactly when. It'll happen in a...

But.

We said that one area will occur next year, but we won't disclose exactly when it'll happen in the.

Speaker 12: in a controlled way blinded, unblinded assessment by the DMC, so we won't know.

In a controlled way blinded unblinded assessment by the DMC, So we won't know.

Speaker 12: when it happened. So at this point,

When it happens so.

At this point.

Speaker 12: Well, I'll be waiting, but we're encouraged by what we're seeing in the potential to study could end early, but however we feel we have a drug that works and we're going to get through a positive A3, at least we're feeling very confident about the ability of the product to get us there. Thank you.

We will all be waiting, but we're encouraged by what we're seeing and the potential the study could end early but however, we feel we have a drug that works. So we're going to get through a positive phase III.

We're feeling very confident about the ability of the product to get us there.

Thank you.

Thank you one moment for questions.

Speaker 1: Our next question comes from June Lee with true security as he may pursue.

Our next question comes from Joon Lee with true Securities You May proceed.

Speaker 13: Hi everyone, this is Mary on for June . So on GTX 1 or 2, for the three patients who begin some loss clinical benefits after reducing. So how do you best plan to highlight this significant observation for regulatory agencies? And easy to at all possible that time to read those could explain some of these clinical benefits. And I have a follow.

Hi, everyone. This is Maggie on for June so on Gtx 102.

For the three patients who.

Regaining some loss clinical benefits after re dosing. So how do you plan to highlight significant observation for Reg.

Regulatory agencies and you see it at all possible that.

To re dose could explain some of these clinical benefits.

Pro forma question.

Speaker 12: Well, first of all, let's talk about what happened to those patients. Those patients got anywhere from one to four doses, five doses.

Well first of all let's talk about what happens to those patients those patients.

Anywhere from one to four doses five doses.

<unk>.

Speaker 12: had their clinical benefit effect with new emerging findings and the safety of it. And then there are off-treatment for, you know, on the order of like two years in which they lost all those activity.

Had there a clinical benefit faxes of newer emerging findings as a safety event.

And then there are off treatment for on the order of like two years in which they lost all of this activity.

Speaker 12: So, with two years off, they're pretty much washed out completely. No drugs, no fit, no benefits.

With two years off theyre pretty much washed out completely no drugs no no benefit so when they start up again theyre really starting back from the beginning and regaining the same functions in terms of the patient. There was one patient who has really gained a lot of words, who had gained 9% to 12 words. The first period is now.

Speaker 12: So when they start up again, they're really starting back from the beginning and regaining the same functions. And in terms of the patient, there's one patient who really gained a lot of words who had gained nine to 12 words in the first period and now having been on consistent therapy for a longer period is actually up to 17 words. And that's the patient also that's now swimming.

Having been on system consistent therapy for a longer period is actually up to 17 words, that's the patient also thats now swimming as well on their own without.

Speaker 12: as well on their own without float support.

Note support.

Speaker 12: We think that the washout period takes them back to the beginning. It's not really, there's no...

So we.

And we think that the washout period takes them back to the beginning it's not really.

There's no relationship between.

Speaker 12: what happened there and redosing effect. If you looked at what happened with naive dosing patients, we showed a graph at Animal State that showed a large number of patients having similar first ever emerging skills, the first time they went on treatment. So we think there's nothing actually specializing on one of those three that's any different from any of the naive treated patients.

What happened there and re dosing effect, if you looked at what happened with nave dosing patients. We showed a graph at analyst day that showed a large number of patients having similar first ever emerging scale is the first time. They went on treatment. So we think theres nothing actually special going over those three that's any different from any of the NIAID treated patients.

Speaker 13: And thank you. The follow-up by is on OI. So are there any specific reasons for preferential suitability of citizen map on AI versus other antiasclusive antibodies like eveenity, SHR 1222 or the others?

Thank you.

Follow up is on Oi. So are there any specific reasons for preferential suitability of sisters of map on AI versus are there.

With an antibody it's Mike.

80 S. H R 12, 22 or the others.

Speaker 12: Well, the only other one is a vet and a room is a vet. Rumble, I guess we call it for short.

Well the only other one is <unk> of that Rommel I guess, we'd call for sure.

Speaker 12: Both target the same sclerosis and there are differences now. Remember, our program to choose a map is a fully human.

Both target the same score us and there are differences, though remember our program to choose the Nab is a fully human antibody, which we think is a better choice for our long term therapeutic because of the risk of anti drug antibodies will be much lower at a fully human antibody we have.

Speaker 12: is a better choice for a long term therapeutic because the risk of anti-drug antibodies will be much lower at a full human antibody. We haven't seen them, so we feel ours is a better choice for chronic therapy.

<unk> seen them, so where we.

We feel ours is a better choice for a chronic therapy, we will have chronic dosing in our label that is <unk> 10. The grubhub. It's only 12 months, we think oi patients need continuous and we've shown when you pull them off drug as was done in the assay Saturday Lee Brown, even with this phosphate onboard, whereas romo has basically given for a year.

Speaker 12: And we've shown when you pull them off drug, it was done in the after, it said they lose brown, even with the phosphonate on board. Whereas, ROMO is basically given for a year and then the supposedly effects are locked in, but with OI, that's not true. You need chronic dosing. So the chronic dosing story will be ours. And finally, when we commercialize, we're gonna provide the...

And then locked.

Supposedly the effects of locked in but with Oi, that's not true you need chronic dosing. So the chronic dosing story will be ours and finally, when we commercialize where we're at.

Speaker 12: First ray patient's important, we do to our rare disease patients, which is not something that's going to happen for an osteoporosis drug.

To provide the first rate patient support we do to our rare disease patients, which is not something that's going to happen for an osteoporosis drugs.

Speaker 13: The last thing I'll mention is the presentation of that drug is a 210 milligrams in a pre-filter inch. It's not very adaptable for different size patients and different amounts of drug dosing, whereas our presentation will allow weak base dosing for each patient and optimization, which I think will be important in the ultimate care of these patients. So, as a sclerosis both can work, but I think ours will be a better choice for long term use. Thank you very much. Thanks for taking our questions.

The last thing I'll mention is the presentation of that drug is a 210 milligrams in a pre filled syringe, if not very adapt over different sized patients in different amounts of drug dosing, whereas our presentation will allow.

Based dosing for each patient and optimization, which I think will be important in the ultimate care of these patients so that.

Anti philosophy, both can work, but I think ours will be a better choice for long term use.

Thank you very much thanks for taking our questions.

Thank you one moment for questions.

Speaker 1: Our next question comes from Mori Raycoff with Guffery D-May Proceed.

Our next question comes from Maury Raycroft with Jefferies. You May proceed.

Speaker 14: Hi, thanks for taking my question. For 701 in Wilson's, what goes into the decision tree for decreasing standard of care? And what is the target reduction in stage?

Hi, Thanks for taking my question for.

For 701, and Wilson's what goes into the decision tree for decreasing standard of care and what is the targeted reduction in stage, one and can you provide more perspective around patient baseline characteristics for the first two cohorts, including baseline cerullo oxidase activity.

Speaker 14: And can you provide more perspective around patient baseline characteristics for the first two chords, including baseline to a little oxidative?

Speaker 12: Yeah, let me pry a little top line and then Eric, if you want to provide a little bit more detail.

Yes, let me try a little top line and then Eric if you want to provide a little bit more detail.

There.

Speaker 12: The trial after they get the drug, there's a period of time where we watch and see how they're doing and then we start titrating down their standard care and the goal in the trials to get them off to our care completely like the first few patients, the others I think are going to get there. I'll let Eric talk a little about what the criteria are. And baseline, we haven't put out all the information in great detail, but maybe Eric, you can provide a little bit of high level on a few things to help with them.

The trial after they get the drug there is a period of time, where we watch and see how they're doing and then we start tight trading down their standard of care and the goal in the trials to get them off Derek Kerr completely like the first two patients the others I think we can get there I'll, let Eric talk a little about what the criteria are at baseline we haven't put out all.

The information in great detail, but maybe Eric you can provide a little bit of high level on a few things to to help with.

Speaker 12: Lori's question. So standard of care or expectation strategy and then be fun.

Laurie's question Phil.

So standard of care, so exploration strategy and then the baseline.

Speaker 5: Yeah, great. It's nice that we're able to do this in open labeled fashion, because it gives us the ability to work closely with these investigators. But the goal really is to give all patients a trial of titration off of current.

Yes, Greg it's nice that we're able to do that it's an open label fashion because it gives us the ability to work closely with these investigators.

But the goal really is to give all patients on trial.

Titration off of current standard of care.

Speaker 5: And what's nice about this disorder is you can monitor copper in a lot of very different ways and certainly with a very big focus on urinary copper, but we feel with all of the types of way we can measure copper. We really do have...

And what's nice about this disorder, you can monitor copper in a lot of very different ways and certainly with a very big focus on urinary copper, but we feel with all of the types of way. We can measure copper when you really do have a good way to understand the effect of the gene therapy, certainly if any patient start seeing any signs and symptoms.

Speaker 5: a good way to understand the effect of the gene therapy. Certainly if any patients start seeing any signs of end symptoms or biomarkers start trending in the wrong way, we will rescue them back to their original dose of key laders and things. But we really haven't seen the need to do that across the border or in a meeting.

Or biomarker start trending in the wrong way, we will rescue them back to their original dose key lasers and thing, but we really haven't seen the need to do that.

Across the border or in a meaningful way.

Speaker 5: The Jerusalem-based activity essay is interesting and again.

So really the plasma based activity assay.

Interesting and again importantly.

Speaker 5: because keyulators in zinc have no effect on that. So the only...

Because key later and Zane Kevin no effect on that so the only.

Speaker 5: So the only way for cerebral plasm to exist is to have copper bound to it. And then with this, as they specifically measuring the loading of copper onto cerebral plasm, these patients are coming in really with...

So the only way for <unk> to exist is to have copper filing to it and then with his assay specifically measuring the loading of copper onto ceruloplasmin. These patients are coming in really with an activity below the more limit of detection.

Speaker 5: and activity below the more limit of detection.

Speaker 4: So thanks again, measuring the rise from there. So still early days patients are definitely still increasing and benefiting from the transgene, but things seem to be really trending in the right direction for the great majority of these patients who have been dose so far. Got it.

Again measuring the rise from there so still early days patients are definitely still increasing and benefiting from the trans gene, but things seem to be really trending in the right direction for the great majority of these patients who had been dosed so far.

Got it that's helpful. Thanks for taking my questions.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from Salveen Richter with Goldman Sachs, he may proceed.

Our next question comes from Silviu <unk> Richter with Goldman Sachs. You May proceed.

Speaker 15: Hi, this is Lydia on for Selvian. Thanks so much for taking our question. So just two on to choose a map. So first, could you just provide a bit more detail on what exactly would trigger an early phase three readout? And then also, do you have any idea on pricing and reimbursement given the availability of by Bostonates and Romo?

Hi, This is <unk> on for Sylvia and thanks, so much for taking our question. So just to answer to reason that so first could you just provide a bit more detail.

On what exactly would trigger an early phase III readouts.

And then also do you have any idea on pricing and reimbursement given the availability of <unk> and round mountain.

Sure so.

Speaker 12: The way the Regis trial was done was at a bent-trivert, and that is the unwinding of the original.

The way the trial is done those are event driven and that is the unwinding of the original.

Speaker 12: Binal primary analysis is driven by having 100% of the fractures required to achieve the information needed.

Final primary analysis is driven by having 100% of the fractures required to achieve the information needed. So it would be event driven and the original idea certainly the areas is to look at 60 and 80% of that maximum assuming a large treatment effect. We think we get hit persuasive statistical significance and maybe just 60% of the Fracs we require.

Speaker 12: So the event driven and the original idea, certainly the era of the look at 60 and 80% of that maximum, assuming a large treatment effect, we think we could hit persuasive statistical significance at maybe just 60% of the fraction required. It's a separation of the two is as high as 67% is noted. So it really depends on the number of fractures and the number of patients in the time of exposure. So it's a complex...

It is the separation of the two is as high as 67% as noted so it really depends on number of fractures and the number of patients at the time of exposure. So it's a complex.

Speaker 12: of those three points. So originally the 100% expected to be somewhere between 12 and 24 months of the exposure to the last patient in. And this would be less than that. But we expect that we would want to see at least nine months of data, of treatments for the last patient in, of our expectations. So it will be fracture dependent, but we would expect to see at least nine months of data from the last patient in.

Those three points. So originally the 100% expected to be somewhere between 12 and 24 months.

Lack of exposure to last patient in and this would be less than that.

But we expect that we would want to see at least nine months of data of treatments for last patient in is our expectation so it'll be fractured dependent but we would expect to see at least nine months of data from the last patient in.

Speaker 3: But that might let me, nine months of exposure to the last patient and at the minimum.

Well that's.

Nine months of exposure the last AGM as a minimum.

Speaker 12: Thanks so much. Oh, yeah, the pricing reimbursement question.

Thanks, so much.

Yes, the pricing reimbursement question.

Speaker 12: Well, obviously, Romo is out there labeled for off-diprosis as a certain price point. It's actually at a lower dose with the way it's used and what we're doing is actually in a much higher dose and will be optimized for OI. So you have to think about the dose differential for the two indications as one feature. The other, of course, is that

Well, obviously romo has out there are labeled for osteoporosis has a certain price point, it's actually at a lower dose with the way it's used and what we're doing is actually a much higher dose and will be optimized for OIS you have to think about the dose differential after the two indications as one feature.

The other of course is that.

Speaker 12: Our treatment will be chronic and so...

Our treatment will be chronic and so.

Speaker 12: The question people will have with the shorter term treatment in residence, whether they should take rum or longer, when it hasn't been given longer, right? I think that becomes more of a barrier question about safety.

The question people have with the shorter term treatment regimens, whether they should take romo longer where it hasnt been given longer right I think that becomes more of a barrier question about safety.

Speaker 12: and we'll have effect the chronic data to charge on candy given that way. We're gonna think hard about our pricing strategy. You know, we've had a work company that looks at

And we will have in fact, the chronic data discharge on can be given that way, we're going to think hard about our pricing strategy. As you know we've had we're a company that looks at.

Speaker 12: you know more moderated responsible pricing as we did for Chris Fita. We think that would make the differential between it and Rommel substantially less and given the dose differential would make it and I think

More moderated responsible pricing as we did for Christy the we think that would make the differential between it romo substantially less and given the dose differential would make it I think.

Speaker 12: a not significant issue for the program. And given our support systems, our delivery home infusion home delivery of drug as we've done to complete it for like 85% of the patient.

Not significant issue.

For the program and given our support systems.

Our delivery home infusion home delivery of drug as we've done for Chris feeder for like 85% of the patients.

Speaker 12: There are going to be a lot of features that will help make this a lot more approachable for our rare disease patients that I don't think they'll get support from. So those are all factors, I think, in how we'll play out. But we're really knowledge about the space because Eric and his team has been commercializing in 90% of those docs we commercialize, could be to to are also treating a lot, right? There's a 90% overlap. So we really know how they are. We have a strong relationship. And that will put us in good position, I think.

They're going to be a lot of features that will help make this a lot more approachable for our rare disease patients that I don't think they'll get support from so.

So those are all factors I think and how it will play out, but we're really knowledge about the space because Eric and his team has been commercializing and 90% of those docs. We commercialized cruceta too are also treating oi right. There is a 90% overlap. So we really know how they are we have a strong relationship and that will put us in.

Speaker 12: to compete and in our view, we'll have the label, we'll have the Beth D'Anna body, we'll have the right do thing, right regimen, the right team to purify. Thanks.

Good position I think to compete and in.

In our view, we will have the label will have the best antibody.

The right dosing regimen, the right team.

Virtualize.

Thanks, so much.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from your own worber with TDK and you may proceed.

Our next question comes from your own Weber with TD Cowen You May proceed.

Great. Thanks, guys for taking the question.

Speaker 16: First, I think a quick one from us.

First I think.

Speaker 16: really kind of looking ahead to your first half of the next year. Obviously you're going to have a pretty busy six months it looks like. So any sense that you can maybe give us on kind of the cadence of when to expect blood, even if it's just kind of relative one before the other would be super helpful.

Quick one from us.

Really kind of looking ahead to your first half of next year. Obviously, you guys have a pretty busy six months it looks like though.

Any sense that you can maybe give us on kind of the cadence of when to expect flat even if it's just kind of relative one before the other would be super helpful.

Speaker 16: And then one quick one on GSD, one I'm sorry if I missed this, but has FDA kind of given you any indication or do you already have a sense of how long after the tough one read out, you really need to continue to follow these patients, really just trying to understand when you might be able or in a position to file and potentially launch.

Then one quick one on GST when I, sorry, if I missed this but.

Has FDA kind of giving you any indication or do you already have a sense of how long after the topline readout you realize that we need to continue to follow these patients.

Really just trying to understand when you might be able to.

Or in a position to file and potentially launch as far along as the data looks good thanks very much.

Speaker 12: So, it gave us a fine and we actually have a table that has some of it. I have to say we've never generally not provided extremely precise target of catalyst for various reasons. It is a busy...

So her caves are fine and we actually have a table that has some but I have to say we've narrowed generally not provided extremely precise target of catalysts for various reasons.

It is a busy first half <unk>.

Speaker 12: So buckier seatbelt, it's gonna be fun. We're gonna have a lot of good work.

<unk> can be fun go on we're going to have a lot of good work.

Speaker 12: and coming out for you, but I don't think I can give you a

And coming out for you, but I don't think I can give you.

Speaker 12: I love how I love exactly when all is going to happen. But we'll have a table that will give you some ideas and it will be fun. I'm looking forward to it because we have.

A blow by blow of exactly when all that's going to happen, but we will have a table that will give you some ideas and.

It will be it'll be fun quarter, I'm looking forward to because we have.

Speaker 12: So many working programs and we're in such a good position. It'll be great to see how they're doing and be able to talk to you about them.

So many working programs and we're in such a good position there it'll be great to see how they're doing and be able to talk to you about them.

Speaker 12: Now, the question on GFD-1 is how long the file, the agreement with FDA is that we could file with 48 weeks of primary data.

Now the question on GST, one is how long the file.

The agreement with FDA that we could file with 48 weeks of primary data.

Speaker 12: and including then long-term extension data from V12 patients, which are now out like five years. So there's quite a bit of data there. So we think we have a lot of long-term durability data in hand, but keep in mind that the trial and roll over a period of a good part of the year. So even if we have 48 weeks from the last patient.

And including then long term extension data from phase one to patients, which are now out like five years. So there's quite a bit of data. There. So we think we have a life long term durability data in hand, but keep in mind that the trial enrolled over a period of good part of the year. So even if we have 40 weeks from the last patient.

Speaker 12: So probably be up to a couple years of data, the very earliest patients by the time we file, right? So I think I would expect us to be able to file within a reasonable time frame. There may be other factors that we'll have to discuss with regard to the rest of the package and filing, but we'll be working to try to file as properly as we can once we get all the pieces together.

They'll probably be up to a couple of years of data the very earliest patients by the time, we file right. So I think.

I would expect us to be able to file within a reasonable timeframe.

There may be other factors that will have to discuss with regard to the rest of the package and filing but we'll be working to try to file as promptly as we can once we get all the pieces together.

Alright, great. Thanks very much.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from Joel Beady with Bear Dimae Proceed.

Our next question comes from Joel Beatty with Baird You May proceed.

Speaker 7: I think for the, okay, for the amalgena spinout, what's the latest plan and timing and how much ownership does all the genics plan to maintain?

Thanks for the update.

<unk>.

Latest plan and timing and how much ownership does astrazeneca plan to maintain.

Speaker 12: Well, we do have a term sheet signed in a group of investors put together that we're filling out that thing to get. I can't tell you more yet about the details, but

Well, we do have.

A term sheet signed in a group of investors put together that we're filling out that seem to get I can't tell you more yet about the details, but our expectation is for <unk> to own the majority interest in the spin out a majority interest in the spin out based on what we would expect but it has not been finalized and I wouldn't want to.

Speaker 12: Our expectation is for all to genics to the majority interest in the spinout, a majority interest in the spinout based on what we'd expect. But it's not been finalized and I wouldn't want to provide any more details that we get closer, but it's moving along. We have a lot of interest, and we'll stay else to prod out some new interest.

Brian you more details when we get closer, but it's moving along we have a lot of interest analyst day also proud out some new interest.

Speaker 12: I think there's a lot of belief that the MAB, small clothes against ammo do work.

I think theres a lot of belief that the mathematical models against <unk> do work.

Speaker 12: But there's also a lot of room for improvement for something better and we think this was one

But there's also a lot of room for improvement for something better and we think this is one.

Speaker 12: good option for how you might do a better treatment. So we'll put out more information we get there, but we don't have a majority interest, and we'll hopefully to fill out that team and get that finance to have much for the end of the year as our goal.

Good option for how you might do.

A better treatment. So we'll put out more information, we get there, but we don't want a majority interest and will hopefully to fill out that team to get that financed happened before the end of the year. It's our goal.

Alright, thank you.

Yes.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from Gene O'Lane with Parklee's Human Proceed.

Our next question comes from Gena Wang with Barclays. You May proceed.

Speaker 8: Thank you for taking my questions. Too very quick.

Thank you for taking my questions.

Two very quick ones. The first one is regarding the <unk> program.

Speaker 8: The first one is regarding the end-to-man program, the update next year. I mean, you said you will also have a 10 patient with longer follow-up.

Next year.

You say you will also have a temptation with longer follow up will you be sure other domains.

Speaker 8: be able to share the babies other doorings. If I look through it's social emotional and also adapt.

Okay.

Shall emotional and adaptive behavior.

Speaker 8: And regarding the multi domain responder index, using a deck could be a possible.

And regarding Dee.

Our multi domain responder index do you think the doctor.

B a possible.

Speaker 8: and maintain support of the professional did and keen.

That you could discuss with FTE about possible approvable endpoint in future and are quickly regarding Chris BD Vita so.

Speaker 8: and quickly regarding Chris Vida. So regarding the in Latin, now the territory will be much more important.

Got.

In Latam now.

Tony will be much more important.

Speaker 8: for the revenue contribution. Any strategy you can think of can improve the penetration there.

The revenue contribution any strategy.

Can think of can improve the penetration there.

Okay.

Well good questions.

Speaker 12: Maybe I'll let, but when I get to you, you can do the, I'll let Eric do the crispy to penetration strategies question.

Well, maybe I'll, let but when I get to are you going to let Eric to the crispy the penetration strategy question.

Speaker 12: All right, I'll start with that first with the agement data. You have to about Bayley, other domains of the Bayley. Allow the means we're not, I think the adapt to the social emotional are not very well designed for agement patients, they're designed for normal people. So I think they're not very good. Well, we will have data on

Alright, I'll start with the first with the <unk> data you asked about daily other domains of the Bailey.

Allows it means we're not I think the adapter the social emotional.

We're not very well designed for Angelman patients are designed for normal people and so I think they are not a very good well we will have data on.

Speaker 12: Adaptive behavior will have vinyl in which has adapt behavior, but we'll also have another scale called ABC scale, and probably I didn't mention, but is an aberrant behavior scale, which I think is...

Adaptive behavior will have buying win which has that favor, but we'll also have another scale called the ABC scale it would probably be.

You mentioned, but is it a barren behavior scale, which I think is maybe even more relevant to these patients for both clinically important.

Speaker 3: Maybe even more relevant to these patients who are both clinically important.

Speaker 12: We talked about social, emotional, or adaptive type things. So we'll have some things, but I don't think the Bailey's not the best test for some of those things. We're focusing on the ones where I think it's sensitive.

You talked about social emotional our adaptive type things. So we'll have some things, but I don't think the.

The Bally is not the best test for some of those things we are focusing on the ones, where I think it's sensitive.

Speaker 12: With regard to the end, so that's 10 patients that we might have longer term data that is up to 256 or longer and 20 that would have day 170. So that's, we're trying to give you a better sense. We'll give you what we have on all of them. Now for MDRI.

With regard to the end so thats 10 patients that we might have longer term data that is up to.

$2 50 for longer in 'twenty that would have day 170, so thats.

We're trying to give you a better sense, we will give you what we have on all of them now for MDI.

Speaker 12: Leave and lead the enterprise a good strategy. We all have FDA's agreement on that. They've cheated. I presented to them, including multi-senior leader in the multiple.

We believe <unk> is a good strategy, we all have fda's agreement on that.

I presented to them, including.

Multiple senior leaders in the multiple conferences.

Speaker 12: and he's publishing a paper on it. It's a very powerful method. I think it's a very appropriate method.

We published a paper on it.

It's a very powerful method I think its a very appropriate method.

Speaker 12: keeping with the under eyes that you really measure endpoints you can agree on anyways endpoints that are meaningful right the only thing the under eye is is an analytical tool how do you take five different endpoints and add up the results and this says look I'm going to add up how many people responded in each of the endpoints

The key thing with the underwriters that you really measure endpoints you can agree on anyways endpoints that are meaningful right. The only thing. They MRI is an analytical tool how do you take five different endpoints that add up the results. In this says look I'm going to add up how many people responded in each of the endpoints to clinically meaningful degree.

Speaker 12: to clinically meaningful degree and add up those responses. It's not conceptually that hard. You do get all the underlying data. So it's not like FD is giving up anything by using that endpoint, right? They're actually getting all the underlying endpoint. So if they can get comfort around the daily scale for certain things, an ASA score, the Barron Fager score, or a violin, or others, as represented about those functions, then I think we can get them comfortable with MBRIs and the MLFIS tool and how to get.

Out of those responses, let's talk conceptually that hard you do get all the underlying data. So it's not like the FDA is giving up anything by even that endpoint right theyre actually getting all the underlying endpoints. So if they can get comfort around the bayley scale for certain things and assay score the Barrett behavior score island or others.

As representative of those functions.

And I think we can get them comfortable with MRI isn't the Nols as tool and how to get to the result.

Speaker 3: So last we'll talk about Chris Vita. Look, I think Chris Vita should be.

So lastly, I talked about Chris fee to look I think Chris feed it should be.

Speaker 4: Majority of peace, in fact, I personally, every single kid who has excellent should be on the feet of not all phosphate if they need treatment. And we still have room to go there. And we're working with our partners on it. I thought maybe Eric, maybe you can say anything we might be doing is try to help them maximize the penetration of the feet of. Well, yeah, just a reiterate. Not cans doing great. It's been very successful. We'll continue with our current commercial efforts.

Majority of peace in fact, I personally think every single Kid, who has <unk> should be on proceed in that oral phosphate if they need treatment.

And we still have room to go there.

And we're working with our partners I thought maybe Eric maybe you can say anything we might be doing to try to help them maximize the penetration of placebo.

Just to reiterate.

Hands doing doing great. It's been very successful thus far will continue with our current commercial efforts.

Speaker 4: really what's going to continue there.

That's really what's going on.

<unk>.

Speaker 4: There's a great but strong demand there is...

The strong demand there.

As is the.

Speaker 4: What's really going to drive the growth there is, as we continue to get formal reimbursement across the other country.

What's really going to drive that.

The growth there is as we continue to get formal reimbursement across the other countries.

Speaker 12: We've seen the significant update just recently in Brazil following the formal reimbursement of the reimbursement. As we work our way through reimbursement through the other countries, we'll see continued broke the Latin American certainly in countries that have started

Alright, we've seen the significant uptake just recently in Brazil, following the formal reimbursement public reimbursement and as we work our way through reimbursement through the other countries.

See continued growth.

Latin American region, certainly in countries that have started treating patients.

Speaker 12: They would like what they see, they start adding patience. So there's a drive for use of the drug. And formerly in Burstwood, it's definitely one of the pieces that will help get us there. It's certainly picked up a lot since Brazil's got approved.

They like what they see they start adding patients. So there is a drive for use of the drug.

<unk> reimbursement is definitely one of the pieces that will help get us there. It certainly has picked up a lot since Brazil got approved.

Speaker 12: I encourage I think there's still more room to grow on Christina still in the middle of launch. It's got flat-towing else to cheer grow.

We're encouraged I think there's still more room to grow and Kristina its still in the middle of launch if not slight plateauing out continue to grow.

Thank you.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from Laura Chico with what would she may proceed?

Our next question comes from Laura Chico with Wedbush You May proceed.

Speaker 17: Good evening. Thanks very much for taking the question. I guess I wanted to circle back on the potential amylogenics spinout. You showed them in treating data at the R&D day with respect to plaque reduction in the 5XFID models. Could you just remind us any data demonstrating effects on either anti-inflammatory, pro-inflammatory markers, their following treatment with the product, and just had a curiosity, will there be any further data updates expected prior to the spinout? It sounds like things are moving along pretty quickly. Thanks very much.

Good evening, thanks, very much for taking the question.

I guess I wanted to circle back on the potential Amyloidogenic spin out and you showed some interesting data at the R&D day with respect to plaque reduction.

Eddie models could you just remind us any data demonstrating effects on either anti inflammatory pro inflammatory markers there following treatment with the product and just out of curiosity will there be any further data updates expected prior to the spin out it sounds like things are moving along pretty quickly thanks very much.

Speaker 12: Yes, we focus mostly on the pharmacology of plaque, rather than secondary markers.

Yes, so we focus mostly on the pharmacology of plaque RASM secondary markers.

Speaker 12: inflammation, etc. So I don't have more to offer you at this point.

Inflammation et cetera, So I don't have more to offer you at this point the one challenge I would say is when you're doing the way you do in the mouth of injecting directly into the brain. There is effect of putting a needle in the brain and how that affects things to get to those models I think you need to be doing real interest equal treatment and maybe in the rat model, where you can do.

Speaker 12: The one challenge I would say is when you're doing what you do in the mouth with jet-conductoring in the brain, there's a fact of putting a needle in the brain how that's...

Speaker 12: To get to those models, I think you need to be doing real inter-stitial treatment. And maybe in the rat model where you can do that, you can kind of look at those markers. But if you have to inject through the brain, I think it makes it a little more complicated to look at those aspects of the neurologic disease.

You can kind of look at those markers, but if you have to inject through the brain I think it's it makes it a little more complicated to get to look at those aspects of the neuro neurologic disease, we believe won't likely put out more data until the spin out occurs we are continuing to do some work, it's not a big burn factor, but there are some <unk>.

Speaker 12: We won't likely put out more data until the spitout occurs. We are continuing to do some work. It's not a big burn factor, but there are some experiments going on to look at.

Parents going on to look at that both the <unk> mouth and.

Speaker 12: They've both a 2XFED mouse and some other aspects of optimization, but we're really encouraged by the potential.

Some other aspects of the optimization, but we're really.

Really encouraged by the potential that we think is greater than the monocline analyzed reducing amyloid in the worst model out there, which is the five X and so we think there is enough interest.

Speaker 12: that we think is greater than the monoclonal analyzed reducing amyloid in the worst model out there, which is the 5XFAD. And so we think there's enough interest.

Speaker 12: with our systems and pinnacle, PC, all-made, actually it really puts us into this actually being able to approach a large market indication which a nice

With our systems and Pinnacle PCL manufacturing it really puts us into this should actually being able to approach a large market indication, which.

And I think it would be.

Speaker 3: from a response we've seen from KOLs in our market work. There's a great deal of interest in something that wouldn't cause area inflammation, but allow a single shot therapy for treatment of a disease of this kind. So we're excited about the spin out and we'll put more information out when we get to get it done. So we progress.

From us the response, we've seen from Kols and our market work there.

A great deal of interest in something that Wouldnt cause area inflammation, but allow a single shot therapy for treatment of diseases. This time. So we're.

We're excited about the spin out and we'll put more information out when we get we get it done as we progress.

Thanks very much.

Thank you.

One moment for questions.

Speaker 1: Our next question comes from Ed Arce with H.E. Wayne Wright. You may proceed.

Our next question comes from Ed Arce with H C. Wainwright you May proceed.

Speaker 13: Hi, good afternoon, everyone. This is Thomas, you're asking a couple of questions for, I appreciate taking our questions. First, perhaps for 114 Santa Leopolds and then, okay, can you discuss some major topics that you're planning to discuss with the FDA and upcoming meeting? And what do you plan to achieve coming up in the meeting?

Hi, Good afternoon, everyone business Thomas Yip, asking a couple questions for Ed I appreciate taking my questions.

Perhaps.

111 for Sanfilippo syndrome.

Can you discuss some major topics.

To discuss with you.

In the upcoming meeting.

What do you plan to achieve coming up the meeting.

Speaker 12: Yeah, well, in the MPS3A program, our main focus of these discussions is on how to qualify effort to self-aid as a biomarker for a clock cell or approval. I point out to you, we're also measuring clinical data and we're encouraged by the clinical data as well. I mean, the patients are continuing to gain ground gain development.

Yes, well in the <unk> program. Our main focus of these discussions is on how to qualify.

<unk> sulfate as a biomarker for accelerated approval.

Pointed out you were also measuring clinical data and.

We're encouraged by the clinical data as well I mean, the patients are continuing to gain ground game development skills over time, and I think that this shows that the gene therapies working while we could potentially get approval by just following these patients clinically.

Speaker 12: skills over time and i think that the shows that the g-d our working well we could potentially get approval by the following the patient clinically our whole but to be able to get

Our hope is to be able to get.

Speaker 12: The biomarker accepted. There's been a challenge for the EG. I think Peter Marx is publicly supported. He used the biomarker, including this biomarker at the recent MPS conference. But we have to get him through the details of how that's done. I think as a company, we're as well versus anyone on how to explain the biomarker and how to analyze the results. But it is a situation where you have a neurodegenerate forward with...

The biomarker accepted this been a challenge for the easy I think Peter marks has publicly supported the use of biomarkers, including this biomarker at the recent MTS conference.

But we have to get them through the details on how that's done I think as a company where as well versus anyone on how to explain the biomarker and how to analyze the results, but it is a situation where you have.

A narrow degenerative floor with.

Speaker 12: a relatively slower progress progression through multiple years. And therefore, the qualification takes a little more work to figure out and support. But I say everything I've seen in our program and multiple other clinical programs and other parties show that these markers.

Relatively slower progress progression through multiple years.

And therefore, the qualification takes a little more work to figure out and support but I'd say everything is seen in our program and multiple other clinical program from other parties show that these markers are represent the underlying disease and their reduction through.

Speaker 12: are represent the underlying disease and their reduction through.

Speaker 12: Either enzyme or gene therapy is showing a medical reduction at wild part, clinical benefit. So we're confident about the value of the treatment and we're continuing to work with them on what it takes to qualify and move ahead.

Either enzyme origin therapy is showing a meaningful reduction in <unk> clinical benefits. So we're confident about the value of the treatment and we're continuing to work with them on what it takes to qualify move ahead.

Speaker 12: I will say for the program, we're also working on the CMC side production because we had to take that over. That is going to take some time. So in any case, we wouldn't be ready to file until we were able to run the CMC side of the equation. This is not a priority program for the company. So we have managed it in a more capital-efficient way, as best we can, given, but our hope would get the CMC straight as well, which will be...

I will say to the progress. We're also working on the CMC side production, we had to take that over that is going to take some time so.

Any case, we wouldn't be ready to file until we were able to run the CMC side of equation. This is not a priority program for the companies that we have managed it in a capital more capital efficient way as best we can given.

But our hope would get CMC straight as well, which will be <unk>.

Speaker 12: Part of the factor will determine our ability to file it in addition to our discussion with the FDA.

Part of the factor will determine our ability to file. It. In addition, our discussion with the FDA.

Speaker 13: And this is perhaps this one more question from us. This one for a GTS one of three for an enduement syndrome.

Perhaps just one more question from us.

This one for GTS model for ethane and human syndrome.

Speaker 13: As we expect the expression call of data in first half of 24, what do you expect the median driven duration among the patients will be and what are your some initial thoughts on possible registration or endpoints?

<unk>.

We expect the expansion cohort data in the first half of 'twenty four.

What do you expect the median treatment duration amongst these patients will be.

<unk>.

Yes.

What are the what are you.

Some initial thoughts on the possible registrational endpoints.

Well the duration.

Speaker 12: Most of the patients 20 will have only day 170. We've shown you that in the most recent extension day, the day 256, or it looks better than day 170.

Most of the patients 'twenty that will show well have only day 170, we've shown you that in the most recent extension data the day $2 54 looks better than day 170.

Speaker 12: However, the dose loading, the average dose loading of the expansion cords is higher than what we just showed you before. So they're actually getting more drug. So, our expectations by gay will tend to see more effect as our expectations.

However, the dose loading the average out floating of extension cords is higher than what we just showed you before so they actually getting more drug.

So our expectations by day, one said, we will see more effect is our expectation.

Speaker 12: We will have 10 patients that should take us through 250, for a lot of the least offense for how that's going and give us an idea. So our expectation for a pivotal study would be that it would be a...

We will have 10 patients that should take us to $2 50.

<unk> will allow us at least a sense for how thats going.

And give us an idea so our expectation for a pivotal study would be that it would be a.

Speaker 12: Somewhere in the range of seven to nine months, kind of study where we've loaded and gone through a few maintenance doses.

Somewhere in the range of 7% to nine months kind of steady, where we loaded and gone through <unk>.

Maintenance doses, we think thats, the sweet spot for improvement and change without giving kids too many placebo interest equal injections.

Speaker 12: We think that's a sweet spot for improvement and change without giving kids too many placebo inter-pequal injections, you know, these are people's kids and you're putting doing one of our punctures in them. So I think that combination will give us enough time to separate and we think it would be long enough. I'm sure the FDA would always want a longer study, but I think we're getting close to the one year point, but I hope that maybe it's gonna be neat to nine months would be.

These are peoples kids and Youre, putting doing lumbar puncture than them. So I think that combination will give us enough time to separate and we think it would be long enough I'm sure. The FDA would always want a longer study, but I think we're getting close to the one year point, but I would hope that maybe it's going to be in the eight to nine months would be.

Speaker 12: A reasonable place to show substantial separation and look at day 2564s kind of a

A reasonable place to show substantial separation and look at day 254 is kind of a.

Speaker 12: place where you can see a lot of movement in the development of these kids.

A place where you could see a lot of movement in the development of these kids.

Got it.

It goes out for taking my questions.

Good.

Speaker 1: Thank you. I'd now like to turn the call back over to Joshua Higa for any closing remarks.

Thank you I'd now like to turn the call back over to Joshua Hager for any closing remarks.

Speaker 13: Thank you. This concludes today's call. If there are any additional questions, please contact us by phone or at irs.orgendx.com. Thank you for joining.

Thank you. This concludes today's call. If there are any additional questions. Please contact us by phone or at IR at <unk> Dot com. Thank you for joining us.

Speaker 1: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.

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