Q3 2019 Earnings Call

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Operator: All participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star and then zero on your touchtone telephone. As a reminder, this call is being recorded. I would now like to turn the conference over to your host, Ms. Sarah Pilgrim.

As a reminder, this call is being recorded I'd now like to turn the conference over to your host Ms. Sara Pellegrino.

Vice President of Investor Relations you may begin.

Operator: Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' third quarter 2019 financial results and corporate highlights. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President and Chief Operating Officer, and Daphne Quimi, Chief Financial Officer. Also joining for Q&A are Dr. Jay Barth, Chief Medical Officer, Dr. Hung Do, Chief Science Officer, and Dr. Jeff Castelli, Chief Portfolio Officer and Head of Gene Therapy.

Good morning, Thank you for joining our conference call to discuss amicus Therapeutics third quarter 2019 financial results corporate highlights speaking on today's call. We have John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President and Chief operating Officer, and Daphne Queenie Chief Financial Officer also joining for today are Dr. Jay.

<unk> Chief Medical Officer, Dr., Hondo, Chief Science Officer, Dr., Jeffrey Donnelly cheap portfolio officer, and head of gene therapy as referenced on slide two we may make forward looking statements within the meaning of the private Securities Litigation Reform Act 1995 relating to our business as well as our plans and prospects.

Operator: As referenced on slide two, we may make forward-looking statements within the meaning of the Private Security Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. However, our forward-looking statements should not be regarded as representations by us that any of our plans will be achieved. Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by none or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the day care of. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the day of this conference call.

Forward looking statements should not be regarded as representation, but at any of our plans will be a cheap.

Any or all of the forward looking statements made on this call may turn out to be wrong. It can be affected by inaccurate assumptions, we might make or by known or unknown risks and uncertainties.

Her cautioned not to place undue reliance on any forward looking statements, which speak only to the date here Oh.

All forward looking statements are qualified in their entirety by the cautionary statement and we undertake no obligation.

This presentation in conference call to reflect events or circumstances activity here.

For a full discussion of such forward looking statements and the risk.

Operator: For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and risk factors section of our annual report on Form 10-K for the year ended December 31, 2018, filed with the Securities and Exchange Commission. The third-quarter press release and materials from today's call, which will be available on our corporate website, and the quarterly report on Form 10-Q for the quarter ended September 30, 2019, to be filed following today's SEC holiday tomorrow. At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer of Amicus. John?

That may impact them, we were free the forward looking statements and risk factor section per annual report on Form 10-K for the year ended December 31st 2018 filed with the Securities and Exchange Commission, the third quarter press release and materials from today's call, which will be available on our corporate website.

And the quarterly report on 10-Q for the quarter ended September Thirtyth 2019 to be filed following todays CCGT holiday tomorrow.

At this time Cds my pleasure to turn the call John Crowley, Chairman and Chief Executive Officer.

Great. Thanks, Sara and welcome everyone to worth third quarter 2019 results conference call I'm pleased to host today's conference call highlights a tremendous effort and progress that we've made it AMAK is during the third quarter and now into the early fourth quarter beginning on slide three.

John Crowley: Great. Thanks, Sarah, and welcome, everyone, to our third quarter 2019 results conference call. I'm pleased to host today's conference call to highlight the tremendous effort and progress that we've made at Amicus during the third quarter and now into the early fourth quarter, beginning on slide three. A month ago, at our Analysts' Day in New York, we grounded everyone in the vision for what we are building, the next great global biotechnology company poised to impact many thousands of people around the world living with rare diseases. To achieve this vision, we are continuing to grow our very successful Gallifold-based business, which Brad will detail in a moment. We are also investing in the advancement of our leading rare disease pipeline, including our Phase III Pompei Biologic, ATGAA, as well as our robust gene therapy pipeline and Portfolio. We are also maintaining a very strong balance sheet and financial discipline to keep us fully funded well into the first half of 2022 through all major upcoming milestones with a clear line of sight to profitability and self-sustainability. So, let me move now to slide number four.

A month ago at our analyst day in New York, We grounded everyone in the vision for what we are building. The next great Global Biotechnology company poised to impact many thousands of people around the world living with rare diseases.

We achieved its vision, we are continuing to grow our very successful Galafold base business, which Brad will detail in a moment.

We're also investing in the advancement of our leading rare disease pipeline, including our phase three pump a biologic 80, G.A. as well as our robust gene therapy pipeline.

And portfolio.

We're also maintaining a very strong balance sheet and financial discipline to keep us fully funded well into the first half of 2022 through all major upcoming milestones with a clear side are probably a line of sight to profitability and self sustainability.

So let me move now to slide number four.

Again as highlighted at the M. It gets analyst day in October and again today, despite the volatility of the financial markets during the third quarter or amick. His team focused intensely on the execution of our plans and the achievement of extraordinary results.

John Crowley: Again, as highlighted at the Amicus Analyst Day in October and again today, despite the volatility of the financial markets during the third quarter, our Amicus team focused intensely on the execution of our plans and the achievement of extraordinary results. For Amicus, the third quarter was another significant period of growth and execution across all of our science, clinical, regulatory, and commercial efforts. Here are the four key takeaways.

Parameters to third quarter was another significant period of growth in execution across all of our science clinical regulatory and commercial efforts.

Here are the four key takeaways.

First galafold continues to be one of the most successful launches for rare disease medicine ever and it remains the cornerstone of our success with 48.8 million in third quarter revenue.

John Crowley: First, Gallup Hold continues to be one of the most successful launches for a rare disease medicine ever, and it remains the cornerstone of our success, with $48.8 million in third-quarter revenue. We are also now treating more than 1,000 patients at a 90% plus compliance and adherence rate. And we have upwardly revised full year 2019 guidance of now $170 million to $180 million. Additionally, all of the global launch metrics that we track are on target or exceeding target, including new patient starts. Compliance and Adherence to Therapy, reimbursement and access, new country approvals, and a broadening prescriber base, among others.

We're also now treating more than 1000 patients added, 90% plus compliance and adherence rates.

And we upwardly revised full year 2019 guidance of now 170 million to $180 million.

All of the global launch metrics that we track are on target, we're exceeding targets, including new patient starts.

Compliance and adherence to therapy.

Reimbursement and access.

New country approvals and a broadening prescriber base among others.

Secondly, following the completion of our strategic business review, our financial outlook is now significantly strengthened with current cash of $514 million.

John Crowley: Secondly, following the completion of our strategic business review, our financial outlook is now significantly strengthened with current cash of $514 million, and Runway Revised now, well into the first half of 2022, getting us on a path to profitability and self-sustainability. Much of our investment in research and development and the infrastructure that we have built around the world to deliver Galliford and to scale up and prepare for approval of ATGAA will also be offset significantly by growing revenues from Gallifold and will also be highly leverageable. Third is ATGAA, that is our Next Generation Enzyme Replacement Therapy for Pompe disease and the crown jewel of our portfolio. This continues its significant momentum toward approval and to becoming what we believe will be the new standard of care for people living with Pompe disease. Today, we are announcing that 100 patients are now enrolled in the pivotal PROPEL study, which remains on track to fully enroll about 120 patients by the end of this year.

And runway revise now well into the first half of 2022.

Getting us on a path to profitability and sell sustainability.

Much of our investment in research and development and the infrastructure that we have built around the world to deliver galafold into scale up and prepare for approval of 80 GA.

We'll also be offset significantly by growing revenues from Galafold and will also be highly leverageable.

Third is 80 G.A. that is our next generation enzyme replacement therapy for pumping disease, and the crown jewel of our portfolio.

This continues its significant momentum toward approval and to becoming what we believe will be the new standard of care for people living with pumping disease.

Today, we are announcing that 100 patients are now enrolled in the pivotable pivotal.

Repelled study, which remains on track to now fully enrolled about 120 patients by the end of this year.

On today's call. We're also reporting that the P. PQ brands have been successfully initiated with our key partner Wishy biologics.

John Crowley: On today's call, we're also reporting that the PPQ runs have been successfully initiated with our key partner, WuXi Biologic. And fourth, finally, our portfolio of gene therapy programs and technologies provides our foundation for the future, and it continues to advance. Advancements here in the third quarter include positive interim data in CLN6 patent disease and the Clinical SAVE CLN3 gene therapy program as well.

And fourth finally, our portfolio of gene therapy programs and technologies provides our foundation for the future and it continues to advance.

Advances here in the third quarter include positive interim data in seal and six batten disease.

A clinical stage C.L., then three gene through three program as well.

We also announced at Analyst day last month that we have selected a highly differentiated pumping gene therapy candidate that is now moving forward into I, India, enabling Tox studies.

Daphne E. Quimi: We also announced at Analyst Day last month that we have selected a highly differentiated Pompe gene therapy candidate that is now moving forward into IND-enabling toxic studies. And as I emphasized at the beginning of the call, we have a very strong balance sheet, financial discipline, and a financial path ahead. The completion of our Strategic Business Review has further strengthened our financial position, which Daphne will highlight in just a moment. This includes savings on operating expenses already realized in the third quarter. We achieve that by taking action with our spending and investments in a number of categories, including operating expenses, including SG&A and R&D; and capital expenditures, including the phasing of capital expenditures. Program Prioritization, and also increased outlook for Galliford and the revenue projections there, all of which will be highlighted today. So with that set up, let me go ahead and turn the call over now to Daphne to review the Amicus financial results, guidance, and outlook. Daphne

And as I emphasize at the beginning of the call. We have very strong balance sheet financial discipline discipline and financial path ahead.

The completion of our strategic business review has further strengthened our financial position, which definitely will highlight and just a moment. This includes savings to operating expenses already realized in the third quarter.

We achieved that by taking actions with our spending and investments in a number of categories.

Including operating expenses to include SGN, a and R&D.

Capital expenses, including the phasing of capital expenditures.

Program prioritization.

And also increased outlook for Galafold in the repartee projection there all of which will be highlighted today. So with that is set up let me go ahead and turn the call over now to Daphne to review the M. It gets financial results guidance and outlook Destiny.

Daphne E. Quimi: Thank you, John, and good morning, everyone. Our financial overview begins on slide 6, with our income statement for the three-month period ending September 30, 2019. For the third quarter of 2019, we achieved gala-fold revenue of $48.8 million, which is an increase of 137 percent over the third quarter of 2018. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 143 percent, offset by a negative currency impact of $1.3 million, or 6 percent. The cost of goods sold is a percentage of net sales, with 11.5% in the third quarter of 2019 as compared to 20.9% for the prior year period.

John and good morning, everyone. Our financial overview begins on slide six with our income statement for the three month period ending September 32019.

For the third quarter 2019, we achieved Galafold revenue of 48.8 million, which is an increase of 137% over the third quarter of 2018. This includes year over year operational revenue growth measured at constant currency exchange rate of 143% offset by a negative currency.

Impact of 1.3 million or 6%.

Cost of goods sold includes manufacturing costs as well as royalties associated with the sale of our product.

Cost of goods sold as a percentage of net sales was 11.5% in the third quarter 2019, as compared to 20.9% for the prior year period.

Daphne E. Quimi: Cost of goods sold as a percent of revenue was favorable as Galliford's revenue continues to grow in the United States, where we do not owe royalties, as well as other countries where we are subject to lower royalties. We continue to make significant investments in R&D and manufacturing with the ongoing pivotal study and commercial scale-up of our Pompeii program, as well as the expansion of our gene therapy portfolio and capabilities. During the third quarter of 2019, we reported $58.9 million in R&D expense, as compared to $138.2 million for the prior year period. The decrease is primarily due to an up-front payment of $100 million for the Cellinex asset acquisition in 2018, partially offset by continued investments in the Pompei Clinical Study Program and our gene therapy pipeline.

Cost of goods sold as a percent of revenue was favorable as Galafold revenue continues to grow in the United States, where we do not over royalty as well as other countries, where we are subject to lower royalties.

We continue to make significant investments in R&D and manufacturing the ongoing pivotal study and commercial scale up in our pump pay program as well is the expansion of our gene therapy portfolio and capabilities.

During the third quarter 2019, we reported 58.9 million in R&D expense as compared to 138.2 million for the prior year period.

The decrease is primarily due to an upfront payment of 100 million for the Selinexor asset acquisition in 2018, partially offset by continued investment in the pump a clinical study program and our gene therapy pipeline.

Total total selling general and administrative expense for the third quarter of 2019 was 39.7 million as compared to 31.9 million for the prior year period. The increase represents the expanded geographic scope of the ongoing galafold commercial launch, including launch activities and Japan Indian.

Daphne E. Quimi: Total selling, general, and administrative expense for the third quarter of 2019 was $39.7 million, as compared to $31.9 million for the prior year period. The increase represents the expanded geographic scope of the ongoing Galliford commercial launch, including launch activities in Japan and the United States. The net loss for the third quarter of 2019 was $61.8 million, or $0.24 per share, as compared to a net loss of $159.2 million, or $0.84 per share, for the prior year period. As of September 30, 2019, we had approximately 254.8 million shares outstanding.

I did state.

Net loss for the third quarter of 2019, 61.8 million or 24 cents per share as compared to a net loss of 159.2 million or 84 cents per share for the prior year period.

As of September 32019, we had approximately 254.8 million shares outstanding.

Turning now to slide seven as John mentioned, we are now fully funded well into the first half of 2022 through the upcoming milestones in our portfolio and continued global growth.

Daphne E. Quimi: Turning now to slide 7, as John mentioned, we are now fully funded well into the first half of 2022 through the upcoming milestones in our portfolio and continued global growth. As part of our normal course of business and considering all the new programs that we have integrated into our organization, we completed a strategic business review where we identified our top priorities and areas of investment to drive efficiencies and cost savings while advancing all our key programs. As a result, we are taking the following actions that will extend our cash runway. We will continue to support Galliford revenue growth and have increased confidence around a higher growth trajectory than we had previously forecast, as Bradley will highlight later. Through our internal teams and contract manufacturing partners, we have identified and are implementing synergies and efficiencies within gene therapy development and manufacturing.

As part of our normal course of business and considering all the new programs that we have integrated into our organization. We completed a strategic business review, where we identified our top priorities and areas areas of investment to drive efficiencies and cost savings.

While advancing all our key programs.

As a result, we're taking the following actions that extend our cash runway.

We will continue to support Galafold revenue growth and have increased confidence around higher growth trajectory than we had previously forecast as Bradley will highlight leader.

Through our internal teams and contract manufacturing partners, we have identified and are implementing synergies and efficiencies within gene therapy development and manufacturing.

We also expect to take a phased approach to build out advocates facilities internal manufacturing and other capital expenditures.

Daphne E. Quimi: We also expect to take a phased approach to build out Amicus facilities, internal manufacturing, and other capital expenditures. Additionally, we plan to continue our prudent gene therapy portfolio management process to support one to two INDs starting in 2021 and beyond. And as we grow, we are leveraging internal resources and external collaborators for measured internal headcount growth through 2022. We have recently begun to implement these measures, and we have already seen some positive impact in the third quarter. Going forward, again, to emphasize, we expect total operating expenses in 2020 to 2022 to remain flat as we firstly leverage the commercial global infrastructure that is already in place for the ATGAA launch and other products in our pipeline, and secondly, transition the costs associated with the development of ATGAA to multiple gene therapy programs in our pipeline.

We plan to continue our prudent gene therapy portfolio management process to support one to two I Andes, starting in 2021 and beyond.

And as we grow we're leveraging internal resources and external collaborators for measured internal head count growth through 2022.

We have recently begun to implement these measures and have already seen some positive impact in the third quarter.

Going forward again to emphasize we expect total operating expenses.

2020 to 2022 to remain flat as we firstly leverage the commercial global infrastructure that is already in place for the 80, G. a launch and other products in our pipeline and secondly transitioned the costs associated with the development of 80 G.A. to multiple gene therapy program.

Our pipeline.

Moving onto slide eight a few comments about our current cash position and 2019 financial guidance.

Daphne E. Quimi: Moving on to slide 8, a few comments about our current cash position and 2019 financial guidance. Cash, Cash Equivalents, and Marketable Securities totaled $514 million at September 30, 2019 compared to $504 million at December 31, 2018. The current cash position and total shares outstanding are inclusive of the June 2019 equity offering. Looking ahead to the remainder of 2019, we are reaffirming our upwardly revised full-year Galliford revenue guidance of $170 million to $180 million, in addition to our non-GAAP operating expense guidance of $410 million to $420 million. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation expense, changes in the fair value of contingent consideration, and depreciation. The total operating expense decreased year over year, and we're slightly down quarter over quarter. Some of these reductions reflected initiatives to moderate our rate of growth and cost control measures that we have taken.

Cash cash equivalents and marketable securities totaled 514 million at September 32019, compared to 504 million at December 31 2080.

The current cash position and total shares outstanding are inclusive of the June 2019 equity offering.

Looking at the remainder of 2019, we are reaffirming our upwardly revised full year Galafold revenue guidance of 170 million to 180 million. In addition to our non-GAAP operating expense guidance, a 410 million to 420 million.

We define non-GAAP operating expense as research and development and SGN expenses, excluding share based compensation expense changes in fair value of contingent consideration and depreciation.

Total operating expenses decreased year over year and were slightly down quarter over quarter.

Some of these reductions reflected initiatives to moderate our rate of growth and cost control measures that we have taken.

We do expect total operating expenses in the fourth quarter to be higher to reflect the initiation of the P. PQ runs at bouchey for 80, GA and the ramp up of gene therapy manufacturing at our CMO partners.

Daphne E. Quimi: We do expect total operating expenses in the fourth quarter to be higher to reflect the initiation of the PPQ runs at WUSHI for ATGAA and the ramp-up of gene therapy manufacturing at our CMO partners. We expect to end the year within the previously stated full-year, non-GAAP operating expense range of $410 million to $420 million. And again, we expect that annual range to remain constant in the years ahead.

We expect to end the year within the previously stated full year non-GAAP operating expense range of 410 to 420 million.

And again, we expect that annual range to remain constant in the years ahead.

Daphne E. Quimi: Considering our anticipated operating expenses and net cash generated from Gallup Hold revenue, we expect to have approximately $420 million in cash at the end of 2019, which provides a runway well into the first half of 2022. On slide 9, I will summarize the key takeaways for our financial outlook, as I highlighted during our analyst day. As mentioned, we are fully funded through upcoming major milestones. We have no financing planned or needed for the remainder of 2019 or the foreseeable future.

Considering our anticipated operating expenses and net cash generated from Galafold revenue, we expect to have approximately 420 million in cash at the end of 2019, which provides a runway well into the first half of 2022.

On slide nine of summarized the key takeaways for our financial outlook as I highlighted during our analyst day.

As mentioned, we are fully funded through upcoming major milestones, we have no financing planned or needed for the remainder of 2019 or the foreseeable future.

We have made significant investments in R&D and DNA to move 80, GNS 80, G.A. through manufacturing and towards the end of its development as well as build our global commercial infrastructure.

Daphne E. Quimi: We have made significant investments in R&D and G&A to move ATGAA through manufacturing and towards the end of its development, as well as to build our global commercial infrastructure. These investments will be largely behind us by the end of 2019, and we believe that this is our peak year for non-GAAP operating expense. As I mentioned earlier, we will leverage the support organization we have built to maximize the value of future program advancements and products with only a modest additional investment required for the ATGAA commercial effort. Our total annual non-GAAP operating expense is expected to remain relatively flat within this $410 million to $420 million range from 2020 to 2022. We expect operating expenses to be significantly offset by the projected $1 billion in cumulative global Galliford revenue over the same three-year period, which Bradley will highlight in a moment. And as we execute what we believe to be the right set of tools, partnerships, and technologies, we are not planning for any significant business development activities in the foreseeable future. I'm happy to address any questions during the Q&A, but for now, I'll turn it over to Bradley to highlight the Galliford launch.

These investments will be largely behind us by the end of 2019, and we believe that this is our peak year for non-GAAP operating expense.

As I mentioned earlier, we will leverage the support organization, we have built to maximize value a future program advancements and products with only a modest additional investment required for the 80 G. a commercial effort.

Our total annual non-GAAP operating expense is expected to remain relatively flat within this for 10 110 million to 420 million range in 2020 to 2020 too.

We expect operating expenses to be significantly offset by the projected 1 billion in cumulative global Galafold revenue over the same three year period, which Bradley will highlight in a moment.

And as we execute what we believed to be the rights set of tools partnership and technologies, we're not planning for any significant business development activities in the foreseeable future.

I'm happy to address any questions during the key money, but for now I'll turn it to broadly to highlight Galafold launch.

Great. Thank you Dan good morning, everyone.

Bradley L. Campbell: Great, thank you Daphne, and good morning everyone. Let me provide more color on the continued growth for Gallifold in the third quarter and on our achievement of 1,000 patients on therapy at the end of 3Q. Our mission at Amicus is to get our medicines to as many patients as quickly as possible, and with this key milestone, we are increasingly confident in the potential to drive Gallifold adoption by thousands of additional patients along the path to $500 million in global sales in 2023 and $1 billion in peak revenue opportunity. Let's begin with a global snapshot on slide 11.

Let me provide more color on the continued growth for Galafold in third quarter and on our achievement.

1000 patients on therapy at the end of Threeq.

Our mission at AMAK guess is to get our medicines to as many patients as quickly as possible and what this key milestone we are increasingly confident the potential to drive galafold, a buck adoption in thousands of additional patients along the path to 500 million in global sales in 2023.

The $1 billion peak revenue opportunity.

Let's begin with the global snapshot on slide 11.

Bradley L. Campbell: Total third-quarter revenue, as has been mentioned, was $48.8 million, again, a year-over-year increase of 137 percent, driven by exceptionally strong momentum in new countries, including the U.S. and Japan, as well as steady growth in our earlier launch countries. Specifically, this reflects $33.4 million, or 68% of revenue generated outside of the United States, and the remaining $15.4 million, or 32%, coming from within the United We have pricing and reimbursement secured in 27 countries around the world, including three new additions this quarter: South Korea, Greece, and Argentina.

Total third quarter revenue as has been mentioned was $48.8 million again, a year over year increase of 137% driven by exceptionally strong momentum in new countries, including the U.S. in Japan as well as steady growth in our earlier launch countries.

Specifically this reflects 33.4 million or 68% of revenue generated outside of United States, and the remaining 15.4 million or 32% coming from within the United States.

We have pricing and reimbursement now secured a 27 countries around the world, including three new additions this quarter.

South Korea grief in Argentina.

We already have the commercial team to support these global approvals and we will continue to pursue opportunities to get Galafold approved and delivered to patients in more countries around the world going forward.

Bradley L. Campbell: We already have the commercial team to support these global approvals, and we will continue to pursue opportunities to get Gallifold approved and delivered to patients in more countries around the world going forward. This ongoing geographic expansion will continue to be an important growth driver, along with continuing to switch patients from enzyme replacement therapy and increasing uptake in the diagnosed untreated market, which I'll highlight more in a moment. Turning now to slide 12, let me comment on the positive momentum across all key global commercial metrics that we're focusing on this quarter. First, at the global level, we estimate Gallifold now has approximately 30% global market share of treated, amenable patients, which is up from 24% in the second quarter, as we continue to add new switch patients as well as previously untreated patients to Gallifold.

This ongoing geographic expansion will continue to be an important growth driver along with continuing to switch patients from enzyme replacement therapy, and increasing uptake in the diagnosed and treated market, which I'll highlight more in a moment.

Turning now to slide 12, let me comment on the positive momentum across all key global commercial metrics that we're focusing on this quarter.

First of the global level, we estimate Galafold now has approximately 30% global market share of treated amenable patients, which is up from 24% in the second quarter as we continue to add new switch patients as well as previously untreated patients to council.

Next as John mentioned compliance and adherence to this world precision medicine continue to exceed 90% globally, reflecting what we think is the strength of the experience that physicians and patients are having with gullible.

Bradley L. Campbell: Next, as John mentioned, compliance and adherence to oral precision medicine continue to exceed 90% globally, reflecting what we think is the strength of the experience that physicians and patients are having with Gallup-Bull. New patient starts continue to be very strong as well, and we continue to see strong performance across the metrics highlighted on this slide in each of our regions, including the U.S., Japan, Europe, and our smaller and mid-sized markets throughout the world. Globally, we're also very encouraged by the increasing number of patients who have been previously untreated. In the medium term, we see that mix approaching 50-50 between Switch and previously untreated patients, and in the longer term, we think a majority of Gallup Hold patients may actually have been treatment-naive prior to the launch of Gallup Hold.

New patient starts continue to be very strong as well and we continue to see strong performance across the metrics highlighted on this slide in each of our regions, including the U.S., Japan, Europe , and our smaller and mid sized markets throughout the world.

Globally. We're also very encouraged by the increasing contribution from previously untreated patients.

And as of September Thirtyth on a global basis, 66% patient on Galafold had switched from enzyme replacement therapy, while 34% were previously not treated this is an important point about 340 of our 1000 plus patients have taken galafold as they're very first tritan for fabry, So we've actually grown.

Overall fabry market in three short years by about 5% as Galafold is increasingly becoming a first line standard of care treatment for fabry patients with amenable mutations.

Bradley L. Campbell: Turning now to slide 13, let me recap the quarterly performance year-to-date that supports our upwardly revised guidance of $170 million to $180 million in global sales. In the third quarter specifically, the increasing contributions of the U.S. and Japan and the continued growth in Europe helped offset some of the uneven ordering patterns that we've seen in the third quarter in previous years. Given the trajectory we're on year-to-date, we think we'll do $50-plus million in GAAP revenue for Q4, which would put us in the middle of that $170- to $180-million revenue guidance range. And remember, that's inclusive of about 4 to 5 million of expected negative cumulative FX impact for the year, which we expect will be about 1 million to 1.25 million in foreign exchange impact each quarter, as Daphne highlighted briefly So again, great performance so far in the base business with strong tailwinds coming into the end of the year. Turning now to slide 14.

In the medium term, we see that mix approaching 50 50 between switch and previously untreated patients and in the longer term. We think a majority of galafold patients may actually have been treatment naive prior to the launch of helpful.

Turning now to slide 13, let me recap the quarterly performance year to date that supports our upwardly revised guidance of 170 million to 180 million in global sales.

In the third quarter, specifically, the increasing contributions of the U.S. in Japan, and the continued growth in Europe helped to offset some of the uneven ordering patterns that we've seen in the third quarter in previous years.

Given the trajectory Ron year to date, we think we'll do 50 plus million in GAAP revenue for Q4, which would put us in the middle of that $170 million to $180 million revenue guidance range and remember that's inclusive of about $4 million to $5 million of expected negative cumulative FX FX impact for the year, which we expect will be about one.

Million to 1.25 million in foreign exchange impact each quarter as Daphne highlighted upon briefly before so again great performance. So far in the base business with strong tailwinds coming into the end of year.

Turning now to slide 14.

John Crowley: With these three years of performance behind us, including the first year of launch now in the U.S. and Japan, we can confidently say we are on a path to that $500 million sales opportunity in 2023. And as I outlined at Analyst Day, we're expecting about a 40% year-on-year growth rate to get to that $500 million. And we expect to generate $1 billion in cumulative revenue between 2020 and 2022 alone, and that goes a long way towards funding the R&D and OpEx that Daphne just described. We also have even more confidence in the $1 billion-plus revenue opportunity peak. And just to put that in context, the global Fabry market was about $1.4 billion in 2018, as the overall Fabry population continues to grow, particularly through the increase in newborn and targeted screening and other diagnostic initiatives, which we're also beginning to invest in.

These three years of performance behind us, including the first year launch now in the less in Japan. We can confidently say, we are on a path to that 500 million dollar sales opportunities in 2023.

As I outlined at analyst day, we're expecting about a 40% year on year growth rate to get to that 500 million.

And we expect to generate 1 billion in cumulative revenue between 2020, and 2022 alone and that goes a long way towards funding the R&D and Opex. The Japanese after you just described.

We also have even further confidence and the $1 billion plus revenue opportunity to peak and just to put that in context. The global Fabry market was about 1.4 billion in 2018 as the overall fabry population continues to grow, particularly through the increase of newborn and targeted screening and other diagnostic initiatives, which we're also beginning to invest.

And finally as a reminder, we have orphan exclusivity in the U.S. in Europe , which alone takes us to the end of the 2000 Twentys.

John Crowley: And finally, as a reminder, we have orphan exclusivity in the U.S. and Europe, which alone takes us to the end of the 2020s, in addition to our Orange Book-listed patents that give us IP coverage into the late 2030s. So with that, let me turn the call back to John to discuss our program updates for ATGAA and Pompeii, as well as our gene therapy portfolio.

In addition to our Orange book listed patents that give us I'd coverage into the late 2000 Thirtys.

So with that let me turn the call back to John to discuss our program updates rate DJ and pump pay as well as our gene therapy portfolio John Great. Thanks, Bradley So as many of you know we just completed a detailed review of our entire portfolio. During our October analyst day. So for today's call I will highlight a few new pieces of information.

John Crowley: John? Great. Thanks, Bradley. So, as many of you know, we just completed a detailed review of our entire portfolio during our October Analyst Day, so on today's call, I will highlight a few new pieces of information and briefly review the key takeaways. Many of the details that we covered at Analyst Day can be reviewed on the event webcast and transcript, which, of course, is available on our website. So I'll begin on slide 16 with our crown jewel, ATGAA for Pompe disease. To remind everybody again, this is the first ever second-generation breakthrough therapy designation for any lysosomal storage disease therapy product, as well as the first and only BTD for Pompe disease ever. We've seen tremendous momentum for what we believe may be the next standard of care, again for a broad population of people living with Pompe disease, and for a product representing what we believe could be a potential $2 billion plus opportunity. There are three new important updates with respect to ATGAA on today's call.

And briefly review the key takeaways many of the details that we covered at the analyst day can be reviewed on the event webcast and transcript which of course is available on our website.

So I'll begin here on slide 16, with our Crown Jewel 80, GA for pump a disease.

To remind everybody again. This is the first ever second generation breakthrough therapy designation for any lysosomal storage disease therapy product as well as the first and only BTD for pump a disease ever.

We've seen tremendous momentum from what we believe maybe the next standard of care again for a broad population of people living with pump a disease and for product, representing but we believe could be a potential $2 billion plus opportunity.

There are three new important updates with respect to 80 GA on today's call.

First we are reporting on the call today that the PQ runs have now begun it will she biologics. These will serve as the foundation for CMC module for a BLA submission, which we continued to anticipate will be for full approval based on the results from the pivotal propelled study.

John Crowley: First, we are reporting on the call today that the PPQ runs have now begun at WUSHE Biologics. These will serve as the foundation for our CMC module for a BLA submission, which we continue to anticipate will be for full approval based on the results from the Pivotal Propel Study. Second, we continue to make great strides in the PROPEL study enrollment, and we have now enrolled the target 100 patients in this study. This is a great achievement.

Second we continue to make great strides in the propelled study enrollment and we have now enrolled the target 100 patients. In this study this is a great achievement.

As mentioned at Analyst day, we're now targeting approximately 120 patients for this study in order to meet the extraordinary demand among physicians and patients across global participating sites.

John Crowley: As mentioned at Analyst Day, we are now targeting approximately 120 patients for this study in order to meet the extraordinary demand among physicians and patients across global participating sites, and we remain on track to complete that enrollment by year end. We also continue our supported studies, including our important pediatric study, to support a broad potential label for ATGAA and Th3rd. We have completed a high-level assessment of the data from our Amicus Natural History Study, known as POM-002.

And we remain on track to complete that enrollment by yearend.

We also continue our supported studies, including our important pediatric study to surprise to support a broad potential label for 18 GA.

And third.

We have completed a high level assessment of the data from our and it gets natural history study known as Tom alluded to.

This is the retrospective natural history study of 100 patients treated with standard of care enzyme replacement therapy, who are matched to the patients treated with 80 GA in our phase II pump a study.

John Crowley: This is a retrospective natural history study of 100 patients treated with standard of care enzyme replacement therapy who are matched to the patients treated with ATGAA in our Phase II Pompeii study. We plan to present the details at an upcoming medical meeting in the first half of 2020. And we plan that this will also support our BLA submission for full approval. Importantly, you should expect that the data in POM-002 will be consistent with the natural history of standard of care enzyme replacement therapy in the published literature. Some of this was highlighted during Analyst Amicus Day in October. As a reminder, our base case remains as a pivotal, propelled study, together with additional data that we've collected in the Phase I-II study to support the full approval of ATGAA. And while we engage with regulators frequently on this program, I'll remind everybody that we will not be providing any color or expectations on any pending or future regulatory interactions until after they have occurred and only if they materially impact our assumptions from this base case.

We plan to present the details at an upcoming medical meeting in the first half a 2020 and we plan that this will also support our BLE submission for full approval.

Importantly.

You should expect you should expect that the data in palm owed to to be consistent with the natural history on standard of care enzyme replacement therapy in the published literature.

Some of this was highlighted during the analyst Amick his day in October .

As a reminder, our base case remains at the pivotal propelled study together with additional data that we've collected in the phase one two study to support the full approval of 80 GA.

And while we engage with regulators frequently on this program.

Remind everybody that we will not be providing any color or expectations on any pending or future regulatory interactions until after they have occurred and only if they materially impact our assumptions from this base case.

We continued to be extremely excited and optimistic about 18 gang as well as our preclinical pumping gene therapy program to build what we believe could be the largest and most valuable franchise in the industry with the potential to offer solutions to all patients living with pump a disease globally.

John Crowley: We continue to be extremely excited and optimistic about ATGAA, as well as our preclinical Pompe gene therapy program to build what we believe could be the largest and most valuable franchise in the industry, with the potential to offer solutions to all patients living with Pompe disease globally. Moving on now to slide 17, I'll highlight our industry-leading portfolio of gene therapies for rare diseases. First in CLN6, we've seen positive interim data in our clinical study that demonstrates meaningful impact of our AAV gene therapy in this devastating form of Batten disease. The positive interim data now includes our initial primary analysis of the combined Hamburg motor and language scores of motor and language function, in addition to the individual component scores on motor, language, seizure, and vision that continue to support the potential for this gene therapy to halt the progression of this devastating fatal neurologic disease The CLN-6 results also provide important read-throughs for our clinical study in CLN-3 Batten disease. Again, CLN3 baton is the most common form of childhood neurodegeneration.

Moving on now to slide 17, I'll highlight here, our industry, leading portfolio of gene therapies for rare diseases.

First and seal and six we've seen positive interim data in our clinical study, which demonstrates meaningful impact of our Avi gene therapy in this devastating form of batten disease.

Positive interim data now includes our initial primary analysis of the combined Hamburg motor and language scores.

Motor in language function. In addition to the individual components scores on motor language seizure envision that continue to support the potential for this gene therapy to halt the progression of this devastating fatal neurologic disease.

Zealand six results provide important read through also for clinical study in CLM three batten disease.

Again Zealand three baton is the most common form of childhood neuro degeneration and.

And in this program, we have safely dose the initial cohort in addition to the patients in our higher dose cohort.

John Crowley: And in this program, we have safely dosed the initial cohort in addition to the patients in our higher-dosed cohort. Also, we have now received EU and U.S. orphan drug designations for both CLN6 and CLN3 batten disease, which together with our CLN1 and CLN8 programs provide a robust Batten disease franchise that may represent $1 billion in peak, recurring revenue and, of course, the opportunity to help thousands of children. As we mentioned at Analyst Day, we have also now declared a Pompe gene therapy clinical candidate to move now into IND-enabling toxicology studies, and this program has the potential to enter the clinic in 2021. Here in this program, we are focused on protein engineering and other work with our colleagues at UPenn to ensure that we can optimize expression, secretion, and targeting so that we may have a wider effective therapeutic window.

Also we have now received you and U.S. orphan drug designation for both CLM six and seal in three batten disease.

Which together with our seal and one in CLL eight programs provide a robust batten disease franchise that combined may represent $1 billion in peak.

Recurring revenue and of course, the opportunity to help thousands of children.

As we mentioned at Analyst day, we have also now declared a pumping gene therapy clinical candidate to move now into I envy, enabling toxicology studies.

This program has the potential to enter the clinic in 2021.

Here in this program, we are focused on protein engineering and other work with our colleagues at U. Penn to ensure that we can optimize expression accretion and targeting so that we may have a wider effective therapeutic window.

And finally, our collaboration with Penn in this collaboration we have an R&D engine, we believed to fuel our future growth with rights to 50, plus diseases, including eight preclinical programs.

John Crowley: And finally, our collaboration with Penn. In this collaboration, we have an R&D engine, we believe, to fuel our future growth with rights to 50-plus diseases, including eight preclinical programs. So now, on slide 18, following these program updates, I'd like to conclude the call with a reminder of our five key strategic priorities, all of which we are on track to meet or exceed. First, the success we've had with Gallifold, as Brad went into detail with our competence in 2019 guidance and the trajectory that it puts us on toward that $500 million in Gallifold sales by 2023, and again, with what we believe is a $1 billion peak Second, again, ATGAA, which remains our crown jewel in our portfolio. We have a high degree of confidence in the data that we've seen.

So now on slide 18. Following these program updates I'd like to conclude the call with a reminder of our five key strategic priorities all of which we are on track to meet or exceed.

First the success, we've had with Galafold is Brad went into detail with.

Our confidence in 2019 guidance in the trajectory that puts us on toward that $500 million in galafold sales by 2023, and again with what we believe as a 1 billion dollar peak potential for Galafold.

Second began 80, GA, which remains our crown jewel of our portfolio.

We have a high degree of competence in the data that we've seen.

Propelled study that Weve enrolled and again now with a very sharp focus on manufacturing we continue to make sure that we have enabled the CMC section of the be a leg.

John Crowley: The propel study that we've enrolled, and again now with a very sharp focus on manufacturing, we continue to make sure that we have enabled the CMC section of the BLA. Also, too, we've seen tremendous progress across our BATN franchise in the clinic, as well as our preclinical gene therapy programs in collaboration with UPenn. And very importantly, too, I'll highlight here our financial strength and financial discipline and now the extension of our cash runway, now well into the first part of 2022. Again, we are fully funded now through all major milestones while continuing to grow the company with no need to raise capital in 2019 or any time soon. We need additional capital. We think that it's in the outer years.

Also to we've seen tremendous progress across our baton franchise in the clinic as well as our preclinical gene therapy programs in collaboration with U. Penn.

And very importantly, two I'll highlight here, our financial strength and financial discipline and now the extension of our cash runway now well into the first part of 2022.

Again, we are fully funded now through all major milestones.

Continuing to grow the company with no need to raise capital in 2019 or anytime soon.

As we need and is.

We need additional capital we think that it's in the outer years and we also believe that that capital could come from multiple non equity sources and non equity linked sources to close what we think is a very small gap on the path to profitability and self sustainability.

John Crowley: And we also believe that that capital could come from multiple non-equity sources and non-equity linked sources to close what we think is a very small gap on the path to profitability and self-sustainability. So on slide 19 here, just to conclude, finally, before we turn the call over to Q&A, I'd just like to focus, again, on the people living with rare diseases. We are fighting to bring new hope and alleviate an enormous amount of suffering for many thousands of people and their families. And we're here to deliver on our mission to these patients and to create significant value for our shareholders. So with that, Operator, we're happy to take questions.

So on slide 19 here just to conclude finally before we turn the call over to Q and add just like to focus again on the people living with rare diseases.

We are fighting to bring new hope and to alleviate an enormous amount of suffering from many thousands of people and their families and we're here to deliver on a mission for these patients and to create significant value for our shareholders. So with that operator, we're happy to take questions.

Ladies and gentlemen, if you have a question. Please press star then the number one I touched on telephone.

Operator: Ladies and gentlemen, if you have a question, please press star, then the number one on your touchtone telephone. At this time, we ask that you only ask one question. If you have any additional questions, please enter back into the queue. If your question has been answered or you wish to move yourself from the queue, please press the pound key. Thank you. Our first question comes from Anupam Rama of J.P. Morgan. Your line is now open.

At this time, we ask that you only ask one question. If you have any additional questions. Please enter back into the queue. If your question has an answer are you wish me for yourself from the Q. Please press the pound key thank you.

First question comes from Rama of Jpmorgan. Your line is that open.

Tessa: Hi all, this is Tessa on this morning for Anupam. Thank you for taking our questions and for the updates here. A few from us on the BATNS program specifically. First, can you remind us of the latest thinking about next steps for the CLN 6 program, specifically with an eye towards regulatory strategy here? And then secondly, for the CLN 3 program with dosing complete, as noted in prior remarks, how should we be thinking about next program updates for CLN 3? Thanks so much.

Hi.

This is tougher on this morning for Oneq. Thank you for taking your questions on for the octane Pierre.

A few from I found the bottom program, specifically first can you remind us that the latest thinking about market stats for the female and sex program, specifically with an eye towards regular regulatory strategy here and then secondly for the CRN free program with dosing concrete as noted.

In prior remarks, how should we be thinking about next program updates first PLM three thanks, so much.

John Crowley: Sure. Thank you, Tessa. So for the questions about CLN6 and CLN3, Jay, I'll let you comment on what we see as next steps there.

Sure. Thank you tested so for the questions for steel and six and CLM Threed Jay I'll, let you comment on what we see as next steps there sure Hello, we kind of course of dose the initial cohort of patients and have.

Jay Barth: Sure. Hello.

Jay Barth: We, you know, have dosed the initial cohort of patients and have also stated that additional patients will be dosed in the CLN6 study with the aim of then engaging the regulators with the data that we have to discuss, you know, steps forward. And that's something that we'll be able to disclose after we've had those interactions. But we plan to move ahead with the clinical study that we have now and actually expand the cohort in that study to include additional patients. That's for CLN6. For CLN3, as John stated before, we have dosed the initial cohort of patients in the low dose, moving towards dosing additional patients in the higher dose cohort with the anticipation that when additional material is available to dose additional patients, presumably at the higher dose, that shows the same safety as we've seen in the low dose. And once again, with the body of data that we get in the Phase 1-2 study, engage regulators with that and discuss, you know, what the regulatory path forward would be for CLN3. And this is something that will happen over the next year.

This is additional patients be dose in the feeling six study.

With the aim of then engaging the regulators with the data that we have to discuss steps forward and that's something that we'll be able to disclose after we've had those interactions, but we plan to move ahead with the clinical study.

We have now and expand actually that cohort in that study to include additional patients that's foresee on six.

Foresee on three we as as John stated before you have dose the initial cohort of patients in the low dose moving towards dosing additional patients and the higher dose cohort.

With the anticipation when additional material is available to dose additional patient.

There's only a fee, but the higher dose.

That shows the same safety as we've seen in low dose.

And once again, all with the body of data that we get in the phase one two study engage regulators with that and discuss what the regulatory.

Path forward would be for sale on three as well and this is something that will happen over the next year.

So TEP is one thing to add to that in addition to all the clinical work and regulatory discussions that Jay as highlighted I'll also highlight a significant amount of the effort in both of these programs now involved the technology transfer, which is well underway for both of these programs to have grammar and Paragon, respectively and a lot.

Jay Barth: So, Tessa, just one thing to add to that, in addition to all the clinical work and regulatory discussions that Jay has highlighted, I'll also highlight the significant amount of the effort in both of these programs now involves the technology transfer, which is well underway for both of these programs, to Brammer and Paragon, respectively, and a lot of the work, again, will focus on all of the CMC requirements that would be necessary to support any PLA filing

Of the work again, we'll focus on all of the CMC requirements that would be necessary to support any L.A. filings here.

Thank you know and our next question comes from two girls Cowen. Your line is now open.

John Crowley: Thank you. And our next question comes from Ritu Baral of Cowan. Your line is now open.

Hi, guys two shots on for its here. Thanks for taking my questions. Just two quick ones from me one on the buttons program Im just wondering how are things going on in terms of building natural history is that really being done by mentioned wise are you considering on cohort and second thing is.

Ritu Subhalaksmi Baral: Hey guys, this is Dushanthan for two. Thanks for taking the time to answer my question. Just two quick ones for me. One on the Batten's program. I'm just wondering, how are things going in terms of building out natural history? Is that really being done by the National Wides, or are you guys also considering your own cohort? And the second thing is, I know you're initiating the PPQ runs with WUSHI. Would there be a possibility for submitting a rolling BLA starting next year? Just wondering how you guys are thinking about that. Thanks.

Missing typically runs a grew she would there be potentially a possibility for submitting a rolling BLE. Starting next year, just wondering how you as Michael pointed out that thanks.

Sure, Jeff if you I'll ask Jeff can steadily our head of gene therapy to talk about the natural history, which we think is going to be very important.

John Crowley: Sure. Jeff, I'll ask Jeff Castelli, our head of gene therapy, to talk about the natural history, which we think is going to be very important as the basis of approval for these BATNs programs. So, Jeff, where are we with both of those? Sure. Good morning. So, I think, as you saw at Analyst Day, we've already provided some of the initial natural history data.

As the basis of approval for these buttons program, So Jeff where are we with both of those pure good morning. So I think as you've seen at analyst day, we've already provided some of the initial natural history data that has all come from nationwide are they havent ongoing study continue to compiled data in that trial.

Jeffrey P. Castelli: That has all come from Nationwide. They have an ongoing study and continue to compile data in that trial. We also have identified several other sources of natural history data. So collectively, we are very optimistic we can get, you know, in the ballpark of 50 patients or so for a natural history data set, which we think will be very robust for doing any kind of natural match comparisons.

We also have identified several other sources of natural history data. So collectively we're very optimistic we can get in the ballpark of 50 patients are so for a natural history data set which we think we'll be very robust for doing any kind of natural match comparisons.

Sure and just to your questions again with the Bbq runs initiated in a heavy focus on the CMC section for 80, GA, we think particularly with the breakthrough therapy designation with this program that there is a potential for a lay a rolling BLA submission to begin but again, we're not going to comment.

John Crowley: Sure. And just to your question, again, with the PPQ runs initiated and a heavy focus on the CMC section for ATGAA, we think, particularly with the breakthrough therapy designation for this program, that there is a potential for a BLA, a rolling BLA submission to begin. But again, we're not going to comment on ongoing discussions with regulators. Once we have clarity on the potential there, we'll be able to provide an update as well.

Don ongoing discussions with regulators once we have clarity on the potential there will be able to provide an update as well.

Joseph Patrick Schwartz: Thank you. And our next question comes from Joseph Schwartz of SBB Learning. Your line is now open.

Thank you and then next question comes from Joseph Schwartz of Leerink. Your line is that open.

Hi, Good morning, guys. Thanks for the update and congrats on all the progress. So two questions for me. This is big on dialing in for Joe maybe for Jim or Jeff.

Daegon Dowling: Hey, good morning, guys. Thanks for the update, and congrats on all the progress. So, two questions for me, this is Daegon Dowling, and for Joe. Maybe for Jay or Jeff, if we could maybe first touch upon Batten's disease. So, when we saw the latest update of the Child Neurology Society presentation, as you mentioned in your prepared remarks, we saw some subscores. Particularly, I was wondering about what your thoughts were with regard to the visual acuity that we saw in three out of the six, I think, older patients that seemed to progress. So, any thoughts on the intravitreal administration of the CLN6 gene therapy? And then, on the second part, with regard to the Pompe gene therapy, can you remind us, is this the same candidate you presented the preclinical data for at ASGCT, and I understand that there are increasing competitive forces sort of coalescing in this area, but any additional data that we can expect to emerge before you enter the clinic, or any specifics you can provide on this Thank you very much.

We can maybe first touch upon buttons disease. When we saw the latest update at the child Neurology Society presentation I'd like you mentioned in the prepared remarks, we saw some sub scores, particularly I was wondering about what your thoughts were with regards to the visual acuity that we saw on three out of a six I think its older pace.

And that seemed to progress.

So any thoughts on Intravitreal administration steel and six gene therapy, and then on the second part.

With regards to the pump a gene therapy can you remind us is this a same candidate you presented the preclinical data for it as GCG.

And I understand if there is increasing competitive forces sort of coalescing in this area, but any additional data that we can expect to emerge before you enter into the clinic, where any specifics that can provide on this candidate. Thank you very much.

Yeah, Jay ill take the first part with the additional data for Baton that we showed in at the child neurology.

Jay Barth: Yeah, Jay, I'll let you take the first part with the additional data for BATMS that we showed at Child Neurology.

Jay Barth: I'll do, yes, to bring everyone up to speed a bit on what was.., presented at Child Neurology Society a couple of weeks ago that you're referring to, it was both more granular data on the hemorrhage motor and language subscores, which both combined and separately, which showed stabilization both in the combined motor and language, plus each component individually, motor and language, are very consistent with one another, showing that the effect of the gene therapy on the patients most profoundly in the younger patients, but in almost all of the patients as well, when compared to natural history, match comparison in terms of slowing the progression of the disease or, frankly, stabilizing it. That was in the motor and language.

If spring everyone up to speed a bit on what was.

Presented a child neurology side, the couple of weeks ago that you're referring to it was both more granular data on the number of motor and language sub scores, which both combined and separately, which showed stabilization both in the combined motor language plus each component individually motor and language or very consistent with one another.

There.

Showing that the effect of the gene therapy on the patients most per family in the younger patients but in.

Almost all of the patients as well when compared to natural history matched comparison in terms of slowing the progression of the disease or frankly stabilizing it.

That was in the motor in language the additional new data we're on the vision scale within the Hamburg and as seizure scale within the Hamburg, both showed general stabilization or a.

Jay Barth: The additional new data were on the vision scale within the Hamburg and a seizure scale within the Hamburg. Both showed general stabilization or a slowing of progression of the disease. A caveat, and I think we said at the time for the visual scores on the Hamburg, is that this is just one. It's the first data that we have on vision available, but there will be more data related to visual acuity and other visual tests that will be coming up in the future, so we'll share that when we have that analyzed as well. And on the seizure subscale as well, showing stabilization of seizure activity in all but the most advanced patients. So that was what we had shown. Now, let Jeff comment on the other question about intrabitrial or other. Yes, so, you know, there actually is a published preclinical manuscript with our CLN6 gene therapy showing an improvement in the eye in animal studies.

Following a progression of the disease, a caveat and I think we said at the time for the visual scores on the hamburgers that is just one that's the first data that we have on the vision available, but there will be more data related to visual acuity and other visual tests that will be coming up in the future. So we'll share that when we have that analyzed.

As well and on the seizure subscale as well showing stabilization of seizure activity in all but the most advanced patients.

That was what we had shown I'll, let Jeff comments on the other question about intravitreal or other.

Ministration.

So they are actually is a published preclinical manuscript with our sale in six stream therapy, showing an improvement in the island in the animal studies. So we are hopeful that the initial interest equal treatment can at least partially addressed division defects and as we continue to see more data, we'll assess if there could be a benefit of of adding an additional.

Jeffrey P. Castelli: So, we are hopeful that the initial intrathecal treatment can at least partially address the vision defects, and as we continue to see more data, we'll assess if there could be a benefit of adding an additional route down the line. Right now, we're optimistic that the intrathecal approach will have an improvement across all the different functions. And like we've seen, older patients may continue to decline some, whereas we hope to see a really more effect in the younger kids in terms of stabilization.

Based on the line right now we're optimistic that.

Intrathecal approach will have an improvement across all the different functions and like we've seen ordered older patients may continue to decline some whereas we hope to see really.

More effective younger kids in terms of stabilization.

Okay, Great Yeah, I'll just comment on the second question then for the pumping gene therapy dig on yes. This is the initial data that we presented at the gene therapy meeting in Washington back in April again, this was something that we and Jim Wilson and his team. We're incredibly pleased to see these results that we presented back in April we continued free.

John Crowley: Great. Yeah, I'll just comment on the second question then for the Pompe gene therapy dig-on. Yes, this is the initial data that we presented at the gene therapy meeting in Washington back in April. Again, this was something that we and Jim Wilson and his team were incredibly pleased to see these results that we presented back in April. We continued preclinical proof of concepts through the summer and into the early fall, and then, of course, we had the additional data that we showed at Analyst Day that allowed us to declare this as the candidate to move forward with.

Clinical proof of concepts through the summer into the early fall and then we of course, we have the additional data that we showed at analyst day that allowed us to declare this as the candidate to move forward here.

John Crowley: Look, there are a lot of people now involved in Pompe gene therapy, which I think is excellent. I think it offers a lot of promise to people living with Pompe. It kind of takes me back to, you know, 21 years ago when I read my first paper on Pompe gene therapy, and now, after all these years, to finally see people moving forward, I think is a very good thing. What we're doing at Amicus, though, is a very differentiated approach to gene therapy here, and what our goal is is to provide a complete approach to addressing this disease through gene therapy through many steps that we've These include protein engineering to optimize secretion, expression, and targeting to key tissues of disease. That includes muscle and, very importantly, CNS targeting to reach the motor neurons. Again, Pompe is a neuromuscular disease and a disease of motor neurons. So those steps, coupled with what we believe to be the optimal promoter and the right vector, could lead to a highly differentiated program and something we're very eager now to move forward with.

Look there are lot of people now involved in pump a gene therapy, which I think is excellent I think it offers a lot of promise to people living with pump pay.

Kind of takes me back to a.

21 years ago, when I read my first paper and pump a gene therapy and now after all these years to finally see people moving forward I think it's a very good thing what we're doing it amick is though is a very differentiated approach to a gene therapy here and with our goal is is to provide a complete approach to addressing this disease through June .

Mean therapy through many steps that we've taken with Dr. Wilson and his team. These include the protein engineering to optimize accretion expression and targeting to key tissues of disease that includes muscle and very importantly, CNS targeting to reach that in motor neurons again pump pay is a new.

Well muscular diseases and disease of motor neurons. So those steps coupled with what we believed to be the optimal promoter in the right vector we think could lead to a highly differentiated program and something we're very eager now to move forward.

Thank you and our next question comes from Mohit.

Mohit Bansal: Thank you. And our next question comes from Mohit Bansalas, from City. Your line is now open.

Citi. Your line is now open.

Keith: Hi there, this is Keith from MOHID, and thanks for taking our questions and, of course, congratulations on the progress this quarter. I just wanted one quick question for you, could you walk us through what the R&D and cash runway guidance reflects as we approach the end of 2019 and then for the flat year over year guidance for 2020? What beyond the current programs is baked in, or should we expect higher spending in connection with expanded programs, particularly with respect to the agreement with Penn? Thanks.

Hi, there this is Keith on promo hasn't thanks for taking your question this and of course, congrats on the progress this quarter.

One quick question for you could you walk us through what the R&D in cash runway guidance reflects as we approach. The other 2019, and then for the flat year over year guidance for 2020.

Beyond the current programs as they can or should we expect higher spending in connection with expanded program.

Particularly with respect to the agreement with them. Thanks.

Sure I think we're pretty clear on the call that we'll have we're happy to repeat it definitely do you want to tackle those sure. So so whats.

What's included in the.

R&D spend is are the key priorities that John .

John Crowley: Sure, I think we were pretty clear on the call, but we're happy to repeat it. Daphne, do you want to tackle these?

Discussed at the beginning of the call, which will which is to continue to move HPG a forward through approval.

Daphne E. Quimi: Sure. So what's included in the R&D spend are the key priorities that John mentioned. All of that is included in the cash runway guidance as well as the operating expense guidance that we've given.

And then focus in on our gene therapy pipeline. So all of the all of that spend is included in the cash runway guidance as well as the operating expense guidance that we've given yeah again, I think you definitely I just want to be perfectly clear again, what we're doing now weve laid the foundation with through.

John Crowley: Yeah, again, thank you, Daphne. I just want to be perfectly clear, again: what we're doing now is we've laid the foundation through very significant investments in R&D for our crown jewel, ATGAA, and we've also made some early investments in gene therapy. With the R&D expenses, the significant amount that we've invested over the last couple of years, that total dollar amount, you should expect to remain relatively flat in the coming years. And, you know, ATGAA is a very expensive program, the largest lysosomal study and the most expensive, I'm sure, lysosomal study ever conducted, again, to fund this crown jewel. That spending now is going to be able to be redeployed as ATGAA moves from clinical development toward approval and commercialization.

Very significant investments in R&D for Crown Jewel for 80, GA and we've also made some early investments in gene therapy with the R&D expenses the significant amount that we've invested over the last couple of years that total dollar amount you should expect to remain relatively flat in the coming years and.

18 gig is a very expensive program the largest lysosomal study and the most expensive onshore lysosomal study ever conducted again to fund this crown jewel.

That spending now is going to be able to be redeployed as HPG a moves from clinical development toward approval and commercialization. We can take the expenditures their move them to multiple gene therapy programs, depending on the gene therapy program. We can fund five to 10 clinical stage.

John Crowley: In addition, on the SG&A side, we've enabled a very capable, highly capable commercial organization now globally to deliver Gallifold successfully. It's now preparing in the early stages for a launch of ATGAA. When we launch ATGAA, we think we need to hire maybe 20 additional people globally to support that, so effectively remaining flat, so highly leverageable infrastructure. So, with all of that, you know, this year, again, operating expenses, SG&A, and R&D, at $410 million to $420 million. We're very confident we'll come in in that range. And that range should be one that lasts for at least the next three years, through the end of 2022, to reflect the advancement of all these programs.

Gene therapy programs, including all the R&D necessary to support these programs for.

So the 80 GA program. In addition on the SGN Ace side, we've been able to very capable highly capable commercial organization now globally to deliver galafold successfully it's now preparing in the early stages for launch for 80 GA. When we launched TJ, we think we need to hire maybe.

20, additional people globally to support that so effectively remaining flat so highly leverageable infrastructure, so with all of that.

This year again operating expenses SGN a in R&D at 400 tend to 420 million very confident will come in in that range and that range should be one that carries forward for at least the next three years through the end of 2022 to reflect the advancement of all these programs.

Earl Basalva: Thank you. And again, ladies and gentlemen, if you do have a question at this time, please press star then 1 on your touchtone telephone. And our next question comes from Earl Basalva of H.C. Wainwright. Your line is now open.

Thank you and again, ladies and gentlemen, if you do you have a question at this time. Please press Star then one I touched on telephone.

Next question comes from solve of H.C. Wainwright. Your line is that open.

Bradley L. Campbell: Hi, good morning. Thank you. Most of our questions have already been answered, but I had a quick housekeeping question. So, is there any significant room to lower your cogs from the 12% range given the anticipated volume growth? Thanks.

Hi, Good morning. Thank you most of all questions have been answered already but I had a quick house keeping question.

So.

Is there any significant room to lower your Cogs from the 12% range given the anticipated volume growth. Thanks.

Bradley L. Campbell: Yeah, the only thing we'd say is, from a manufacturing perspective, it's a pretty steady state process at this point, and distribution as well. The one place where you see a little bit of movement, as Daphne highlighted, is in royalties. Our royalties are limited to ex-U.S. geographies, and so as the U.S. and non-royalty-producing countries continue to be a higher contribution of sales, you might see that number creep down a little bit. Really, that's just a function of the distribution of revenue between royalty and non-royalty. We should not expect further savings from an operating cost of goods perspective.

Yes, the only thing we'd say is from a manufacturing perspective, it's a pretty steady state process at this point and distribution as well the one place where you see a little bit of movement as Daphne highlighted is in the royalty our royalties are limited to ex us geographies and so.

As the U.S. and non royalty.

Reducing countries continue to be a higher contributions of sales you might see that number creep down a little bit it really thats just a function of of the distribution of revenue between royalty and non royalty we should not expect further savings from a operating costs of goods perspective.

Thank you know at our next question comes from Youngstown Janney. Your line is open.

Youngfound: Thank you. And our next question comes from Youngfound of Janey. Your line is now open.

Hi, thank him for two questions. So the question since on them Homepay gene therapy program.

We have you talked about.

John Crowley: you talked about the potential additional animal species for preclinical study and also alternative routes of administration. So I wonder, do you think IV is still the best way to deliver the vaccine and do you plan to study the candidate in, for example, non-human primates? And also, at which point do you plan to disclose what kind of AAV capsid that is? Thank you.

Potential additional animal species for preclinical study and also alternative route of administration. So I Wonder do you think.

He is still the best way to deliver and do you plan to study the Kennedy and for example, nonhuman primates and also at which point do you plan to disclose what kind of baby.

Cuts that that is thank you.

Jeffrey P. Castelli: Sure, I'll ask Jeff Castelli to field that.

Sure I'll ask Jeff can sell lead to feel that yes sure. So we are moving forward with all of our preclinical I, enabling studies, which will include primate studies.

Jeffrey P. Castelli: Yeah, sure. So we are moving forward with all of our preclinical INE-enabling studies, which will include primate studies. As we've mentioned before, we are definitely going to address the CNS aspects or look to address the CNS aspects. While we've seen in our mouse studies that IV administration led to a robust impact in the CNS, as we go through those primate studies, we might determine that we need to do a combination of IV plus intrathecal to make sure we address the CNS, and we will provide that data as we have it. But right now, we're really excited by the overall construct and its potential, whether it's dose IV alone or IV plus intrathecal.

As we mentioned before we are.

Definitely going to address the CNS aspects or look to address the CNS aspects, while we've seen in our mouse studies that IB administration led to robust impact in the CNS as we go through those primate studies, we might determine that we need to do a combination of Ivy plus intrathecal to make sure we addresses CNS and we will.

Provide that data as we have it but right now we're really excited by the overall construct and its potential whether its dosed IB alone or Ivy plus intrathecal.

Salveen Jaswal Richter: Thank you. And our next question comes from Salveen Richter of Goldman Sachs. Your line is now open.

Thank you Yeah, and then next question comes from.

Goldman Sachs. Your line is that open.

Andrea: Thanks for taking our questions. This is Andrea from Salveen. My first one is, when you think about your goal of moving GALFOLD use from mostly switch patients to predominantly treatment-naive patients, can you help us understand the gating factors to achieving this transition?

Thanks for taking your question. This is Andrew on for Salveen on My first one is when you think about your goal of living Galafold piece from mostly switch patients to.

Predominantly treatment naive patients can you help us understand the gating factors to achieving this transition.

Bradley L. Campbell: [inaudible]

President Please yes, sure and remember we still have quite a bit of room left to grow from a switch perspective.

Bradley L. Campbell: Bradley, please. Yeah, sure. And remember, we still have quite a bit of room left to grow from a switch perspective. The U.S. and Japan, as an example, are more recently launched countries, and our strategy has always been to focus on the switch patients first, because they're the ones that are already in the system. They're getting treated every other week with an alternative therapy. And so that's the initial population, and there are lots of switch patients still to move. That being said, in our more mature launch markets, we're starting to see roughly equal rates of growth from switch and naive patients, and I think there are a number of things there. First of all, again, those patients are not coming in every other week for their infusion, so you have to reach out to those patients through their physicians.

You asked in Japan as an example are more recently launched countries and our strategy has always been to focused on the switch patients first because they're the ones that are already in the system. They are getting treated every other week with with an alternative therapy and so that's that's the initial population and theres lots of switch patients still the move.

That being said in our more mature launch markets, we're starting to see roughly equal rate of growth from switch and naive patients and I think there are number of things. There first of all again those patients are not coming in every other week for their infusion. So you have to reach out to those patients through the physicians I think also as experienced build.

Bradley L. Campbell: I think also, as experience builds with the product, that gives physicians and patients more confidence to take a therapy, a relatively new therapy, as their first treatment for Fabry disease. And obviously, also, it's a big factor in the diagnosis rates we're seeing. We continue to see a 10 to 20% diagnosis rate in Fabry disease, and that's driven by newborn screening, targeted population screening, and other diagnostic initiatives. So that will also contribute to the increasing rate of previously untreated patients coming to Galliford.

With.

Product that gives physicians and patients more confidence to take a therapy, a relatively new therapy as their first treatment for their fabry disease and all obviously also it's a big factor of the diagnosis rates were seeing we continue to see attendant to 20% diagnosis rate in fabry disease.

That's driven by newborn screening targeted population screening other diagnostic initiatives. So that will also contribute to that increasing rate of.

Previously untreated patients coming onto to Galafold.

John Crowley: Thank you. And at this time, I would now like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks.

Thank you and at this time I would now like to turn the conference back to Mr., John Crowley, Chairman and CEO for closing remarks.

Operator: Great. Thank you, Operator. Thank you all for listening. Again, a very, very successful quarter, and again, we remain focused on delivering on our mission for patients and for shareholders. Thank you for listening. Have a great day.

Great. Thank you operator, thank you all for listening again, a very very successful quarter and again, we remain focused on delivering on our mission for patients and for shareholders. Thank you for listening I have a great day.

Operator: This concludes today's conference call. Thank you, and have a great day.

This concludes today's conference call. Thank you and have a great. Okay.

Operator: BF-WATCH TV 2021