Q2 2019 Earnings Call

After the 2019 results, conference call, and webcast. At this time, 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, then zero on your touchtone telephone.

At this time all participants are in a listen only mode.

Later, we will conduct a question and answer session and instructions will follow what that time.

If anyone should require assistance during the conference. Please press Star then zero on your Touchtone telephone.

Operator: As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Ms. Sarah Pellegrino, Vice President of Investor Relations and Corporate Communications. You may begin. Good morning.

As a reminder, this conference call is being recorded.

I would now like to turn the conference over to your host.

MS Sara Pellegrino, Vice President of Investor Relations and corporate Communications you may begin.

Good morning, Thank you for joining our conference call to discuss and it gets therapeutics second quarter 2019 financial results and corporate highlights.

Operator: Thank you for joining our conference call to discuss Amicus Therapeutics' second quarter 2019 financial results and corporate highlights. Speaking of 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.

Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer.

Bradley Campbell, President and Chief operating officer, and Daphne cleaning Chief Financial Officer.

Also joining for culinary or Dr., Jay Barth, Chief Medical Officer, Dr., Hondo, Chief Science Officer, and Dr., Jeff Castelli, Chief 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 of 1995 relating to our business as well as our plans and prospects.

Speaker: As referenced on slide 2, we may make forward-looking statements within the meaning of the Private Securities 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 known or unknown reasons. You are cautioned not to place undue reliance on any forward-looking statement, which speaks only to the date hereof. 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 date hereof. 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 10-2.

Our forward looking statements should not be regarded as representation by us that any of our plans will be achieved.

And your old 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 known or unknown risks and uncertainties.

You are cautioned not to place undue reliance on any forward looking statements, which speak only to the date hereof.

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 date hereof.

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 factor section of our annual report on Form 10-K for the year ended December 31st 2018 filed with the Securities and Exchange Commission and the quarterly report on Form 10-Q for the quarter ended June Thirtyth 2019 to be filed today at this time. It is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer John .

Speaker: for the year ended December 31st, 2018, filed with the Securities and Exchange Commission, and the quarterly report on Form 10-Q for the quarter ended June 30th, 2019, to be filed today. At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer.

John Crowley: Great. Thanks, Sarah, and welcome, everyone, to our second quarter 2019 results conference call. I'm pleased today to host this conference call to describe more fully with our team the great progress that we've made at Amicus during the second quarter and early into the third quarter this year. It was a great quarter for Galliford in what continues to be one of the most successful launches for rare disease medicine ever. This success for Gallup Hold now puts us on a clear path to achieving our commercial objectives in 2019, but it also lays the foundation for this oral precision medicine to reach as many patients as quickly as possible for many years to come. Yalopold continues to be the cornerstone of our success at Amicus, and it will also support the advancement of our robust pipeline, including ATGAA for Pompe disease and what is now the industry's largest rare disease gene therapy portfolio, So, let me go through the highlights here.

Great. Thanks, Sarah and welcome everyone to our second quarter 2019 results conference call I'm pleased today to host this conference call to describe more fully with our team the great progress that we've made it damages during the second quarter and really into the third quarter. This year.

It was a great quarter for Galafold in what continues to be one of the most successful launches for a rare disease medicine ever.

This success for Galafold now puts us on a clear path to achieving our commercial objectives in 2019, but it also lays the foundation for this world precision medicine to reach as many patients as quickly as possible for many years to come.

Galafold continues to be the cornerstone of our success at Energous and it will also support the advancement of our robust pipeline, including 80 GA for pump a disease.

And what is now the Industrys largest rare disease gene therapy portfolio, which are all highlighted on slide three so let me go through the highlights here.

First there has been continued strength in global revenue and adoption for Galafold.

Speaker: First, there has been continued strength in global revenue and adoption for Gallifold, with Q2 being the highest quarter of growth since launch. We are reiterating our full year guidance of $160 million to $180 million, and we announced this morning that we now expect to surpass our target of 1,000 patients on Galafold well before the end of this year. 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 approval, and a broadening prescriber base, among others. Specifically, with respect to compliance and adherence, we continue to see exceptionally high rates, with Galliford continuing now at more than 90% globally. Indeed, the vast majority of patients who have gone on to Gallifold remain on Gallifold for several years now in some cases. We have also captured 24% of the global market share of treated amenable Fabry patients with an increasing proportion of previously untreated patients, now driving that growth, which Brad will cover further in this call.

With Q2 being the highest quarter of growth since launch.

We are reiterating our full year guidance of 160 million to $180 million and we announced this morning that we now expect to surpass our target of 1000 patients on Galafold well before the end of this year.

All of the global launch metrics that we track are on target for exceeding target, including.

New patient starts.

Compliance and adherence to therapy.

Reimbursement and access.

New country approval.

And the broadening prescriber base among others.

Specifically with respect to compliance and adherence we continue to see exceptionally high rates.

With Galafold, continuing now at more than 90% globally.

Indeed, the vast majority of patients who have gone onto Galafold remain on Galafold for several years now in some cases.

We have also captured 24% of the global market share of treated amenable fabry patients with an increasing proportion of previously untreated patients now driving that growth, which Brad will cover further in this call.

Second.

Speaker: Highlighting the momentum with the enrollment and the opening of new sites in our global Pompeii pivotal study known as the PROPEL study, and now with the majority of patients enrolled in this PROPEL study, we are well on track to complete enrollment by year-end. Third, we just last week announced the positive two-year interim clinical results for our CLN6 Batten disease gene therapy, showing the potential to halt the progression of a devastating fatal neurologic disease in children. Next is the expanded pen collaboration, which we announced in Q2, and which we will also highlight in this poll today. Again, this provides Amicus with the industry's largest rare disease gene therapy portfolio, including the majority of all lysosomal disorders and more prevalent rare diseases through this collaboration with UPenn. And finally, I'll highlight the strength of our balance sheet, which we added to in Q2 with the $200 million equity financing to further advance our portfolio and add important new investments in biologics and gene therapy manufacturing while providing cash runway into 2021.

Highlight is the momentum with the enrollment in the opening of new sites in our global pump a pivotal study known as the propelled setting.

And now with the majority of patients enrolled in this propelled study.

We are well on track to complete enrollment by year end.

Third we just last week announced the positive two year interim clinical results for our seal and six batten disease gene therapy, showing the potential to halt the progression of a devastating fatal neurologic disease in children.

Next is the expanded pen collaboration, which we announced in Q2 and which we will also highlight on this call today.

Again this provides advocates for the industry's largest rare disease gene therapy portfolio, including the majority of all lysosomal disorders.

And more prevalent rare diseases through this collaboration with U. Penn.

And finally, I'll highlight the strength of our balance sheet, which we added to in Q2 with the $200 million equity financing.

To further advance our portfolio and an important new investments in biologics and gene therapy manufacturing.

While providing cash runway into 2021.

And in addition, as we highlighted in the press release. This morning, we have entered into an agreement with Ultragenyx to enlighten exclusive Japanese rights to MEP SEBI for MPS seven are rare lysosomal disorder in Japan.

John Crowley: And in addition, as we highlighted in the press release this morning, we have entered into an agreement with Ultragenyx to license the exclusive Japanese rights to Mepsevi for MPS-7, a rare lysosomal disorder, in Japan. There is true alignment here between both amicus and ultragenics in the best interest of people living with MPS7 in Japan, where we believe that we can leverage our existing amicus infrastructure, relationships, and experience in clinical development, regulatory approvals, and commercialization within lysosomal disorders, and I'll highlight that further on this call. So with that overview, let me go ahead and hand the call over to Bradley Campbell, our President and Chief Operating Officer, to highlight the very successful Galliford launch that continues.

There is true alignment here between both amick isn't ultragenyx in the best interest of people living with MPS seven in Japan.

We believe that we can leverage our existing AMAK has infrastructure relationships and experience in clinical development regulatory approvals and commercialization within the lysosomal disorders and I'll highlight that further on this call. So with that overview. Let me go ahead and hand, the call over to Bradley Campbell, our President and Chief operating officer to highlight the very successful Galafold launch that continues Brent.

Bradley L. Campbell: Great. Thank you, John. Good morning, everyone.

Great. Thank you John good morning, everyone.

Operator: Good morning, everyone.

Let me begin on slide five with our snapshot of the Galafold launch through June Thirtyth, we remain very pleased with the strong revenue growth this quarter adoption and launch trajectory of council.

Bradley L. Campbell: Let me begin on slide 5 with our snapshot of the Gallifold launch through June 30th. We remain very pleased with the strong revenue growth this quarter, adoption, and launch trajectory of Gallifold. And as John noted, Gelfold continues to be one of the most successful rare disease drug launches ever, and we're confident that this strength will continue throughout the remainder of 2019 and beyond. Our second quarter revenue was $44.1 million, which is a year-over-year increase of approximately 107% from the second quarter of 2018. This was the highest quarter of growth since.

And as John noted Galafold continues to be one of the most successful rare disease drug launches ever and we're confident that this strength will continue throughout the remainder of 2019 and beyond.

Our second quarter revenue was $44.1 million, which is a year over year increase of approximately 107% from the second quarter of 2018. This was the highest quarter of growth since launch.

We continued to see exceptionally strong momentum in new countries, including the us in Japan.

Bradley L. Campbell: We continue to see exceptionally strong momentum in new countries, including the U.S. and Japan, as well as in our earlier launch countries. We have pricing and reimbursement secured in 24 countries around the world. And following the recent approval in Argentina, we're now preparing to launch in our first ever market in Latin America, which is a very important geography for us, where we see the potential to deliver Galafold to many more Fabre patients living with amenable mutations. Additionally, we see continued strength of the approved Galliford label, with 348 amendable variants included in the U.S. and 367 amendable mutations in Europe, with most other labels And remember, we had around 260 mutations in the original European label, so we've added almost 100 new mutations to the label since launch, and that number should continue to grow.

As well as in our earlier launch countries.

We have pricing and reimbursement secured in 24 countries around the world.

And following the recent approval in Argentina, we are now preparing to launch in our first ever market in Latin America, which is a very important geography for us where we see the potential to deliver galafold to many more fabry patients living with amenable mutations.

Additionally, we see continued strength of the approved Galafold label with 348 amenable variance included in the US and 367 amenable mutations in Europe .

With most other labels based on that M&A submission in the EU.

And remember we had around 260 mutations in the original European level. So we've added almost 100, new mutations to the label since launch and that number should continue to grow.

Moving now to slide six I will provide a little bit more detail on the positive momentum across all key global commercial metrics, we're focusing on this quarter.

Bradley L. Campbell: Moving now to slide six, I'll provide a little bit more detail on the positive momentum across all key global commercial metrics we're focusing on in this course. At the global level, we estimate Gallup Hold now has approximately 24% global market share of treated amenable patients, which is up from 18% in the first quarter, as we continue to add new switch patients as well as previously untreated patients to Gallup Hold. Next, as John mentioned, compliance and adherence to this oral precision medicine continue to exceed 90% globally. This is really important and we think continues to reflect that physicians and patients are having a strong experience with Gallup Hold. In the United States, we are now approaching a year into the launch and continue to see steady growth from a widening prescriber base of now more than 100 physicians.

At the global level, we estimate Galafold now has approximately 24% global market share of treated amenable patients, which is up from 18% in the first quarter as we continue to add new switch patients as well as previously untreated patients to galafold.

Next as John mentioned compliance and adherence to this world precision medicine continue to exceed 90% globally.

This is really important and we think continues to reflect that physicians and patients are having a strong experience with counsel.

In the United States, we're now approaching a year into the launch and continue to see steady growth from a widening prescriber base of now more than 100 physicians.

Bradley L. Campbell: We also see continued broad reimbursement coverage, along with a shorter time from prescription to patients receiving drugs. In our international markets, we continue to see strong growth from the EU5 countries, as well as significant contributions from smaller and mid-sized markets like Australia, Canada, the Nordics, and beyond. And in Japan, we're on track to deliver all of our full-year objectives as well.

We also see continued broad reimbursement coverage along with a shorter time from prescription to patients receiving drug.

In our international markets, we continued to see strong growth from the EU five countries as well as significant contribution from smaller and mid sized markets like Australia, Canada, the nordics and beyond.

And in Japan, we're on track to deliver all of our full year objectives as well.

Globally. We're also very encouraged by the increasing contribution from previously untreated patients, which are now breaking out here for the first time as of June Thirtyth on a global basis, 64% of patients on Galafold had switched from enzyme replacement therapy and 36% were not previously treated again. This trend is right on target with our strategy for higher initial adoption and switch patients at launch.

Bradley L. Campbell: Globally, we're also very encouraged by the increasing number of previously untreated patients who are now breaking out here for the first time. As of June 30th, on a global basis, 64% of patients on Galvold had switched from enzyme replacement therapy, and 36% were not previously treated. Again, this trend is right on this target with our strategy for higher initial adoption in switch patients at launch, followed by increasing penetration into the population of diagnosed untreated patients. So, with the introduction of GALFOLD to the treatment armamentarium for febrile disease, we have grown the number of treated patients by hundreds of patients.

Followed by increasing penetration into the population of diagnosed and treated patients.

So with the introduction of Galafold to the treatment armamentarium for Fabry disease, we now have grown the treated population by hundreds of patients.

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

Bradley L. Campbell: In the medium term, we see this mix approaching 50-50 between switch and previously untreated patients. And in the longer term, we think the vast majority of Gallup Hold patients could actually have been treatment-naive prior to the launch of Gallup Hold. We believe that this trend reflects the shifting paradigm globally where Gallup Hold is increasingly becoming a first-line standard of care. Treatment for Fabry patients with a mental mutation.

We believe that this trend reflects the shifting paradigm globally were galafold is increasingly becoming a first line standard of care.

Treatment for fabry patients with amenable mutations.

And let me just finish by reiterating that new patient starts continued to be very strong and we now expect to exceed our targeted 1000 patients on galafold well before year end.

Bradley L. Campbell: And let me just finish by reiterating that new patients are starting to come in very strong, and we now expect to exceed our target of 1,000 patients on Gallifold well before the year ends. Now, I turn now to slide 7, and I'll comment on our quarterly revenue. Just as we saw in 2018, the first half of 2019 has been in line with our expectations for moderate growth in the first quarter and higher growth in the second quarter. Again, these trends are consistent with Gallup Hold adoption and ordering patterns that we've seen over the past few years.

Let me turn now to slide seven and I'll comment on our quarterly revenue.

Just with as we saw in 2018, the first half of 2019 has been in line with our expectations for moderate growth in first quarter and higher growth in second quarter.

Again these trends are consistent with galafold adoption in ordering patterns that we've seen over the past few years and while we don't give quarterly guidance I'll note that as in previous years. We do continue to expect Galafold revenue to reflect non linear growth in the summer months with those 90 day orders of this world precision medicine place before vacation and holidays, especially in Europe .

Bradley L. Campbell: And while we don't give quarterly guidance, I'll note that, as in previous years, we do continue to expect Gallup Hold revenue to reflect nonlinear growth in the summer months with those 90-day orders of this oral precision medicine placed before vacations and holidays, especially in Europe, and we expect growth to pick up again in the fourth quarter of this year. Turning now to our guidance on slide 8, with the strength and the commercial metrics I just described, we remain highly confident in our guidance range of $160 million to $180 million for the year. Given the strong trajectory to date, we now expect that we'll hit that 1,000-plus patient target well before the end of 2019. And as we highlighted on last quarter's call, and we will reiterate again today, with the majority of our sales continuing to come from outside the United States, we do expect modest foreign exchange headwinds throughout the rest of the year, which we think puts us in the reportable revenue range in the middle of this $160 million to $180 million guidance range.

And we expect growth to pick up again in the fourth quarter of this year.

Turning now to our guidance on slide eight with the strength in the commercial metrics I. Just described we remain highly confident in our guidance range of $160 million to $180 million for the year.

Given the strong trajectory to date, we now expect again, we'll hit that 1000, plus patient target well before the end of 2019 and as we highlighted on last quarter's call and we will reiterate again today with the majority of our sales continuing to come from outside the United States. We do expect modest foreign exchange headwinds throughout the rest of the year, which we think puts us in the reportable revenue range in the middle of this 160 million to $180 million guidance range.

With this strong momentum we also remain very confident the galafold will achieve $500 million in sales globally by 2023.

And finally on slide nine we continue to believe that Gail that fabry disease may be one of the most under an mis diagnosed human genetic disorders in the world.

With the potential to reach $1 billion in sales and peak for Galafold.

The global Fabry market was about $1.4 billion last year, we continue to growth expected in the fabry population, particularly through the increase of newborn screening and other diagnosis diagnostic initiatives, which we are continuing to invest in as well as recent extension of our Galafold IP that now covers treatment methods through the year 2038.

Bradley L. Campbell: With this strong momentum, we also remain very confident that Gallup will achieve $500 million in sales globally by 2023. And finally, on slide nine, we continue to believe that GALF, that Fabry disease, may be one of the most under- and misdiagnosed human genetic disorders in the world, with the potential to reach $1 billion in sales at peak for Gallup Holdings. The global FabRay market was about $1.4 billion last year, with continued growth expected in the FabRay population, particularly through the increase in newborn screening and other diagnostic initiatives which we are continuing to invest in, as well as the recent extension of our Galliford IP that now covers treatment methods through the year 2038. We're even more confident in the potential to impact thousands of people living with FabRay disease who are amenable to this novel precision method. So with that, let me turn the call back to John to discuss our ATGA program in Pompeii, as well as our gene therapy portfolio.

We are even more confident in the potential to impact thousands of people living with fabry disease or amenable to this novel precision medicine.

So with that let me turn the call back to John to discuss our ATM program in pumping as well as our gene therapy portfolio John .

Great. Thanks, Bradley so here on slide 11, as we look to our pump pay program I'd like to take a moment to highlight 18, GAA and that propelled steady as shown in the schematic on this slide which is now this study more than a majority enrolled to include both ERP switch and ERP naive patients.

There has been great interest from patients and physicians and growing momentum here, especially following the two year data presented at the Worldsymposium earlier this year as well as the breakthrough therapy designation or BTD granted by the USS da in the first quarter for 18, Eone late onset pump a disease.

This is the first second generation therapy as well as the first therapy for pumping disease.

Ever to receive this important BTD designation with several key features as outlined on this slide.

Moving to slide 12, let me highlight here the very successful execution.

John Crowley: Thank you all. Great, thanks Bradley. So here on slide 11, as we look to our POMPEI program, I'd like to take a moment to highlight ATGAA and the PROPEL study, as shown in the schematic on this slide, which now has more than a majority enrolled to include both ERT switch and ERT nave patients. There has been great interest from patients and physicians and growing momentum here, especially following the two-year data presented at the World Symposium earlier this This is the first second-generation therapy, as well as the first therapy for Pompe disease, ever to receive this important BTD designation with several key features as outlined on this slide. Moving to slide 12, let me highlight the very successful execution of our Amicus teams around the world in enrolling the Pivotal Propel study. We are now active in 29 countries.

Of our amick his teams around the world in enrolling the pivotal pub propelled study we are now active in 29 countries.

We plan to include all leading global pump a treatment centers to ensure a broad depth of physician and patient experience around the world.

We are on track to complete enrollment by year end with topline data targeted for the first half of 2021.

That propelled study together with the ongoing phase one two study support our strategy to advance 18, GAA as quickly as possible with the potential we believe to become the new standard of care for people living with pumping disease.

As a reminder, our base case remains that the pivotal for pellets study will be the basis together with additional data that we've collected in the phase one two study to support the full approval of 18 gang.

On slide 13 ill summarize the key accomplishments for the ATM AA program in 2019, and reiterated number of our objectives.

Year to date, we have presented additional phase one two data out to 24 months again earlier this year at the Worldsymposium in Orlando.

John Crowley: We plan to include all leading global Pompeii treatment centers to ensure a broad depth of physician and patient experience around the world. We are on track to complete enrollment by year-end, with top-line data targeted for the first half of 2021. The PROPEL study, together with the ongoing Phase I-II study, supports our strategy to advance ATGAA as quickly as possible with the potential, we believe, to become the new standard of care for people living with Pompe disease. As a reminder, our base case remains that the Pivotal Propel Study will be the basis, together with additional data that we've collected in the Phase I-II study, to support the full approval of ATGAA. On slide 13, I'll summarize the key accomplishments for the APGAA program in 2019 and reiterate a number of our objectives.

We were granted BTD.

And we have passed the halfway mark on target enrollment in our pivotal study.

For the remainder of this year, we are on track to achieve target enrollment in the propelled study. We also plan to present six month safety and functional data from most all of the patients in the fourth cohort as well as the complete 24 month data from our first three cohorts in our phase one two study at the World Muscle Society in Copenhagen in early October . We are also on track to report natural history data this year.

We continue to plan supported studies, including the initiation of our important pediatric study, which we expect to begin in the second half of this year.

And on the manufacturing front in important use of proceeds from our recent equity financing.

Is to accelerate the agreed upon CMC requirements and the very important related manufacturing work together with our partners at Wishy biologics.

John Crowley: Year-to-date, we have presented additional Phase I-II data out to 24 months earlier this year at the World Symposium in Orlando. We were granted BTD, and we have passed the halfway mark on target enrollment in our Pivotal study. For the remainder of this year, we are on track to achieve target enrollment in the PROPEL study. We also plan to present six-month safety and functional data from most all of the patients in the fourth cohort, as well as complete 24-month data from our first three cohorts in our Phase I-II study at the World Muscle Society in Copenhagen in early October. We are also on track to report natural history data this year.

And while we engage with regulators frequently 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 material impact materially impact our assumptions from our base case.

We continue to be extremely excited about 18 gang as well as our preclinical pump paid 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 to slide 14, let me provide some more color on our recent deal with Ultragenyx, where again, we have in licensed exclusive Japanese rights to MEP SEBI for MPS seven in Japan.

John Crowley: We continue to plan supportive studies, including the initiation of our important pediatric study, which we expect to begin in the second half of this year. And on the manufacturing front, an important use of proceeds from our recent equity financing is to accelerate the agreed-upon CMC requirements and the very important related manufacturing work together with our partners at WuXi Biologic. And while we engage with regulators frequently, 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 our base case.

There is true alignment here again between both amethyst and ultragenyx in advancing and treatment and in the best interest of MPS seven community in Japan.

With our existing AMAK is infrastructure relationships and experience in clinical development regulatory approvals and commercialization in the lysosomal field. We believe we can leverage our experience in galafold commercialization and February and pumping clinical development.

To support what is a very small number of patients in an investigator sponsored study.

This small study in Japan, together with the existing data package from previously completed clinical studies.

That is supported MEP SEBI approvals in other countries is expected to support Ajay an NDA submission.

John Crowley: We continue to be extremely excited 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 to slide 14, let me provide some more color on our recent deal with Ultragenyx, where again we have in-licensed exclusive Japanese rights to Mepsevi for MPS7 in Japan. There is true alignment here, again, between both amicus and ultragenics in advancing a treatment and in the best interest of the MPS7 community in Japan. With our existing Amicus infrastructure, relationships, and experience in clinical development, regulatory approval, and commercialization in the lysosomal field, we believe we can leverage our experience in Gallifold commercialization and Febrez and Pompei clinical development to support what is a very small number of patients in an investigator-sponsored study.

There is no upfront payment tier and there will be no material impact to our budget assumptions to bring forward. This new program, which we believe has the potential to make a very meaningful impact for people living with MPS seven in Japan.

I commend that.

Dr able cacace and the team at Ultragenyx for their unwavering commitment to the highest quality science into patients and we're happy to be their partner for this mission in Japan.

Moving on now to slide 16, I'll highlight here, our industry, leading portfolio of gene therapies for rare diseases, which weve assembled in less than a year to combine the leading gene therapy technologies products and mines in this field.

We added significantly to this portfolio during the second quarter with the expanded agreement with Dr., Jim Wilson and the University of Pennsylvania that is detailed on slide 17.

As you'll see here on slide 17. This expanded collaboration with you Pan reflects the extraordinary scientific capabilities at AMAK is as well as the success that we have seen with the work that we've done already in collaboration with Dr. Wilson and his team at U. Penn.

John Crowley: This small study in Japan, together with the existing data package from previously completed clinical studies that have supported MEP-SETI approval in other countries, is expected to support a JNDA submission. There is no upfront payment here, and there will be no material impact on our budget assumptions to bring forward this new program, which we believe has the potential to make a very meaningful impact on people living with MPS-7 in Japan.

Underlying this collaboration is the guiding objective to combine the AMAK is protein engineering platform.

With the pen gene transfer technologies and capabilities to replicate the initial preclinical success. We have had so far with preclinical proof of concept for our gene therapy and pump a disease.

Again, there are three elements to this collaboration first.

John Crowley: I commend Dr. Emil Kakas and the team at Ultragenyx for their unwavering commitment to the highest quality science and to patients, and we're happy to be their partner for this mission in Japan. Moving on now to slide 16, I'll highlight here our industry-leading portfolio of gene therapies for rare diseases, which we've assembled in less than a year to combine the leading gene therapy technologies, products, and minds in this field. We added significantly to this portfolio during the second quarter with the expanded agreement with Dr. Jim Wilson and the University of Pennsylvania that's detailed on slide 17.

AMAK has acquired the right to a majority of all lysosomal disorders for all of next generation 10 gene therapy technologies.

Second the existing collaboration which we announced in October of 2018.

Has now been expanded from three to six immediate programs for rare genetic diseases.

With the extension of the agreement and existing programs in on pain disease Fabry disease in CDK IL five deficiency disorder.

We now add these diseases.

Niemann pick type C MPS three b as well as the next generation program for MPS III.

And finally, the third element of this program is the next generation research agreement tier.

John Crowley: As you'll see on slide 17, this expanded collaboration with UPenn reflects the extraordinary scientific capabilities at Amicus, as well as the success that we have seen with the work that we have done already in collaboration with Dr. Wilson and his team at Penn. Underlying this collaboration is the guiding objective to combine the Amicus Protein Engineering platform with Penn Gene Transfer technologies and capabilities to replicate the initial pre-clinical success we've had so far with pre-clinical proof of concept for our gene therapy in Pompe disease. Again, there are three elements to this collaboration.

This provides amick us with exclusive.

Disease specific worldwide rights to collaborate with the gene therapy program at Penn.

To develop potentially disruptive new gene therapy platform technologies and programs.

For 12 additional pre specified rare diseases.

Including more prevalent rare disorder populations, such as Rett syndrome Angelman syndrome.

Myotonic dystrophy, and select other muscular dystrophies, where in many cases, we can incorporate the AMAK is protein engineering expertise in targeting mutations to enable cross correction to many of them. While also utilizing pens next generation gene delivery technology.

John Crowley: First, Amicus acquired the right to a majority of all lysosomal disorders for all next-generation pen gene therapy technologies. Second, the existing collaboration, which we announced in October of 2018, has now been expanded from three to six immediate programs for rare genetic diseases. With the extension of the agreement and existing programs in Pompe disease, febrile disease, and CDKL5 deficiency disorder, we now add these diseases: Neiman Pick Type C, MPS 3B, as well as the Next Generation Program for MPS 3A.

Turning now to slide 18. In addition to the significant momentum across all of our pen programs. We also reported our first set of clinical data for gene therapy platform license from nationwide children's.

The details of this data set were highlighted in the press release and conference call last week, but I'll briefly highlight the five key takeaways that give us great excitement in the potential for our gene therapy for CLM six patent disease as well as our broader platform of Intrathecal Avi gene therapies.

John Crowley: And finally, the third element of this program is the Next Generation Research Agreement tier. This provides Amicus with exclusive disease-specific worldwide rights to collaborate with the gene therapy program at Penn to develop potentially disruptive new gene therapy platform technologies and programs for 12 additional pre-specified rare diseases, including more prevalent rare disorder populations such as Rett syndrome, Angelman syndrome, myotonic dystrophy, and select other muscular dystrophies, where, in many cases, we can incorporate the Amicus protein engineering expertise in targeting mutations to enable cross-correct Turning now to slide 18, in addition to the significant momentum across all of our PEN programs, we also reported our first set of clinical data for a gene therapy platform licensed for nationwide children.

First.

Is the meaningful impact that we saw on motor and language function.

Again in children with this fatal neurologic disease that Rob Rob them rapidly of their ability to walk speak C and think.

Second is the evidence now of disease stabilization in seven of the eight and children with data at up to approximately two years post gene transfer.

Third is the newly available data on an untreated natural history cohort or all 14 at a 14 patients progressively lost language in motor function over the same period of time.

Indeed, it's remarkable that many of these children treated with gene therapy in our study continued to be able to walk in speed when the natural history suggests that they would have lost the ability to speak and moved into a wheelchair or have become bedridden.

Fourth is the compelling data comparing siblings living with CLM six batten disease, including three children treated in this study who had untreated siblings.

As well as two pairs of siblings that were treated in this study.

John Crowley: The details of this data set were highlighted in a press release and conference call last week, but I'll briefly highlight the five key takeaways that give us great excitement about the potential for our gene therapy for CLN6 patent disease, as well as our broader platform of intrathecal AAV gene therapies. First is the meaningful impact that we saw in motor and language function, again in children with this fatal neurologic disease that robs them rapidly of their ability to walk, speak, see, and think. Second, there is now evidence of disease stabilization in seven out of eight children with data at up to approximately two years post-gene transfer. Third, there is newly available data on an untreated natural history cohort where all 14 out of 14 patients progressively lost language and motor function over the same period of time.

And fifth business is the favorable safety profile seen with the Intrathecal dose of Avi that was administered to all of these patients in the study.

We also believe the interim clinical results validate the broad potential of the advocates intrathecal Avi platform in other forms of batten disease, including our own gene therapy for CLM, three batten disease, which is in the clinic.

And we remain on track to enroll the high dose cohort and to complete enrollment in this clinical study for CLM three batten disease by the end of this year.

And again as we announced a few weeks ago, we have partnerships now in place with the leading contract manufacturing organizations in gene therapy. In addition to plasmin suppliers for our CLM six gene therapy program and initial clinical and preclinical gene therapy programs. So with that important summary, let me go ahead, now and turn the call over to our Chief Financial Officer depth, Mcqueeney, who will review our second quarter 2019 results Stephanie.

John Crowley: Indeed, it's remarkable that many of these children treated with gene therapy in our study continue to be able to walk and speak when the natural history suggests that they would have lost the ability to speak and moved into a wheelchair or have become bedridden. Fourth, the compelling data comparing siblings living with CLN6 Batten disease, including three children treated in the study who had untreated siblings, as well as two pairs of siblings that were treated in this study. And fifth, the favorable safety profile seen with the intrathecal dose of AAV that was administered to all of these patients in this setting. We also believe the interim clinical results validate the broad potential of the Amicus intrathecal AAV platform in other forms of Batten disease, including our own gene therapy for CLN3 Batten disease, which is in the clinic.

Thank you John and good morning, everyone.

Our financial overview begins on slide 20, with our income statement for the three month period, ending June 32019 for the second quarter of 2019, we achieved galafold revenue $44.1 million, which is 107% increase over the second quarter of 2018.

This includes a year over year operational revenue growth measured at constant currency exchange rates of 115% offset by negative currency impact of $1.7 million or 8%.

John Crowley: And we remain on track to enroll the high-dose cohort into complete enrollment in this clinical study for CLN3 Batten disease by the end of this year. And again, as we announced a few weeks ago, we have partnerships now in place with the leading contract manufacturing organizations in gene therapy, in addition to plasmid suppliers for our CLN6 gene therapy program and initial clinical and preclinical gene therapy programs. So with that important summary, let me go ahead now and turn the call over to our Chief Financial Officer, Daphne Quimi, who will review our second quarter 2019 results.

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

Cost of goods sold as a percentage of net sales was 12.2% in the second quarter of 2019 as compared to 14.7% for the prior year period.

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 overall LTL 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 in our pump pay program as well as the expansion of our teen therapy portfolio and capabilities.

Daphne E. Quimi: Thank you, John, and good morning, everyone. Our financial overview begins on slide 20 with our income statement for the three-month period ending June 30, 2019. For the second quarter of 2019, we achieved Gallup Gold revenue of $44.1 million, which is a 107 percent increase over the second quarter of 2018. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 115 percent, offset by a negative currency impact of $1.7 million, or 8 percent. Cost of goods sold includes manufacturing costs as well as royalties associated with the sales of our products. Cost of goods sold as a percentage of net sales was 12.2% in the second quarter of 2019 as compared to 14.7% for the prior year period. Cost of goods sold as a percent of revenue was favorable as gallifold 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.

During the second quarter of 2019, we recorded $71 million in R&D expense as compared to $34.7 million for the prior year period.

This increase was attributed to investments in our 88 pump a clinical program as well as the clinical and preclinical gene therapy programs that we added to the pipeline in the second half of last year.

Total selling general and administrative expense for the second quarter of 2019 was $42.6 million as compared to $29.2 million for the prior year period.

The increase represents the expanded geographic scope of the ongoing galafold commercial launch, including launch activities in Japan, and the United States.

Net loss for the second quarter of 2019 was $84.6 million or 36 cents per share as compared to a net loss of 61.8 million or 33 cents per share for the prior year period.

And as of June 32019, we had approximately 254.5 million shares outstanding.

Moving on to Slide 21, a few comments about our current cash position and 2019 financial guidance.

Cash cash equivalents and marketable securities totaled $575.7 million at June 32019, compared to 504.2 million at December 31 2018.

Daphne E. Quimi: 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 second quarter of 2019, we recorded $71 million in R&D expenses as compared to $34.7 million for the prior year period. This increase can be attributed to investments in our ATGAA Pompe clinical program, as well as the clinical and preclinical gene therapy programs that we added to the pipeline in the second half of last year. Total selling, general, and administrative expense for the second quarter of 2019 was $42.6 million as compared to $29.2 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 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 full year galafold revenue guidance of 160 million to $180 million.

Taking into account our anticipated investments as well as anticipated net cash generated from Galafold revenue. We expect we expect to have approximately $400 million in cash on the balance sheet at the end of 2019.

This projected year end cash balance reflects all ongoing investments in our operations.

Including Pompei manufacturing scale up and facilities, including our new Global research and gene therapy Center of excellence in Philadelphia.

With our current cash position and anticipated net cash generated from Galafold revenue, we have sufficient capital to fund ongoing operations into 2021.

As we have noted in the past to potential future business development collaborations pipeline expansion and investment in manufacturing capabilities may impact our future capital requirements.

This summarizes our key financials for the second quarter of 2019.

Daphne E. Quimi: The net loss for the second quarter of 2019 was $84.6 million, or $0.36 per share, as compared to a net loss of $61.8 million, or $0.33 per share, for the prior year period. And as of June 30, 2019, we had approximately 254.5 million shares outstanding. Moving on to slide 21, a few comments about our current cash position and 2019 financial guidance. Cash, cash equivalents, and marketable securities totaled $575.7 million at June 30, 2019, compared to $504.2 million at December 31, 2018. 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 full-year Gallup Gold Revenue Guidance of $160 million to $180 million. Taking into account our anticipated investments, as well as the anticipated net cash generated from Gallifold revenue, we expect to have approximately $400 million in cash on the balance sheet at the end of 2019.

Additional details can be found in our quarterly report on Form 10-Q .

I'm happy to address any questions during the Q and eight but for now I will turn it back to John .

Great. Thank you Daphne I'll conclude this morning's call by highlighting.

The five key strategic priorities on slide 23 that we outlined at the beginning of the year, which we are on track to meet or exceed.

First with the strength of our global launch of Galafold. We again are highly confident in our full year 2019 guidance range of $160 million to $180 million.

Second pump pay and our ATP GA program continue to be a top priority.

Now with the majority of patients enrolled in our propelled pivotal study.

And with new data from our phase one two clinical study to be present to be presented at the world muscle Society in October .

Third we are we already reported the positive interim clinical data and CLM six batten disease clinical setting and we remain on track to fully enroll the steel industry Batten disease study this year.

Our fourth goal is to achieve preclinical proof of concept for our Fabry gene therapy program as well as additional preclinical data for our pump pay gene therapy program.

This pump a gene therapy program is advancing ahead of schedule and we anticipate selection of a clinical candidate in 2019 to move into R&D, enabling studies.

Daphne E. Quimi: This projected year-end cash balance reflects all ongoing investments in our operations, including Pompeii Manufacturing Scallop and facilities, including our new Global Research and Gene Therapy Center of Excellence in Philadelphia. With our current cash position and anticipated net cash generated from Gallup Gold revenue, we have sufficient capital to fund ongoing operations into 2021. As we have noted in the past, potential future business development collaborations, pipeline expansion, and investment in manufacturing capabilities may impact our future capital requirements. This summarizes our key financials for the second quarter of 2019. Additional details can be found in our quarterly report on Form 10-Q. I'm happy to address any questions during the Q&A, but for now, I will turn it back to John.

And finally, we are committed to maintaining our financial strength.

Our cash runway is sufficient to fund our operating plan into 2021.

Advancing several years closer toward our 2023 vision to treat 5000 patients and achieve $1 billion plus in global revenue.

And then on slide 24, a snapshot of the many milestones already achieved so far with many more to come throughout the remainder of this year, so with that operator, I'll hand, the call back to you for Q Vinay. Thank you.

Ladies and gentlemen, if you have question at this time. Please press the Star then.

The number one key on your Touchtone telephone.

If there are questions has been answered audio was storing more yourself from the queue.

Daphne E. Quimi: Great. Thank you, Daphne.

Please press the pound key.

Thank you.

John Crowley: I'll conclude this morning's call by highlighting the five key strategic priorities on slide 23 that we outlined at the beginning of the year, which we are on track to meet or exceed. First, with the strength of our global launch of Gallup Hold, we are again highly confident in our full year 2019 guidance range of $160 million to $180 million. Second, Pompeii and our ATGAA program continue to be a top priority, now with a majority of patients enrolled in our PROPEL Pivotal Study and with new data from our Phase I-II Clinical Study to be presented at the World Muscle Society in October. Third, we have already reported positive interim clinical data from the CLN6 Batten Disease Clinical Study, and we remain on track to fully enroll the CLN3 Batten Disease Study this

Your first question comes from the large enough on the form Rama from JP Morgan. Your line is now open.

Hey, guys. Thanks, so much for taking my question and congrats on all the progress here.

I was wondering if we could just revisit the ceiling six update from last week and we've gotten this question a couple times. After the uptake can you remind us of the scope of the natural history uptake will be getting later this year and.

How should we be thinking about the age distribution in that natural history dataset. Thanks, so much.

Sure. Thanks out of home I'll ask Jay Barth, our chief Medical officer to handle that.

Right now we have the natural history data we presented on.

Approximately 14 patients that will continue to view the data set.

John Crowley: Our fourth goal is to achieve preclinical proof of concept for our FEBRE gene therapy program, as well as additional preclinical data for our POMPEI gene therapy program. This pump A gene therapy program is advancing ahead of schedule, and we anticipate selection of a clinical candidate in 2019 to move into IND-enabling studies. And finally, we are committed to maintaining our financial strength. Our cash runway is sufficient to fund our operating plan into 2021, advancing us several years closer toward our 2023 vision to treat 5000 patients and achieve one billion dollars plus in global revenue. And then on slide 24, a snapshot of the many milestones already achieved so far, with many more to come throughout the remainder of this year. So with that, operator, I'll hand the call back to you for Q&A. Thank you.

For now as we continue to expand that.

Natural history data, that's a process that will happen over time, so it's hard to pin down exactly when we'll have.

Larger numbers on that.

But from the natural history data that we have currently.

There is a clear overlap of the ages of the patients in the treated cohort versus the natural history cohort.

That's the basis of the comparison that we showed between the two.

In which all 14 of the natural history patients declined at least two points on reverse as opposed to just one of the eight treated patients over approximately two years a clear differentiation.

Great. Thanks, so much Oh I'm sorry, yes, we're also comment on the ages.

We expect in any future natural history study there will be a broad range of ages as we have now of the.

14 the.

And atrocities that that we have now covers a broad range at similar to the treated patients.

And that'll continue to be the case in the larger expanded natural history dataset. Once we have that assembled but it will also include quite a number of younger children as well as a whole so longer tail, yes, yes.

Operator: Ladies and gentlemen, if you have a question at this time, please press the star and then the number 1 key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound. Thank you. Your first question comes from the line of Anupam Rama from JP Morgan.

On upon that makes sense.

Great. Thanks, so much for taking my questions. Thank you very much.

Your next question comes from the line of Frito borrow from Cowen. Your line is now open.

Anupam Rama: Your line is now open. Hey guys, thanks so much for taking the question and congratulations on all the progress here. I was wondering if we could just revisit the CLN6 update from last week, and we've gotten this question a couple times after the update. Can you remind us of the scope of the natural history update we'll be getting later this year, and how should we be thinking about the age distribution in that natural history data set? Thanks so much.

Good morning, guys. Thanks for taking the question.

Can I start with the some of the.

Marketing strategies for Galafold now that your percentage of naive patients seems to be growing in picking up momentum.

Is there a profile of these sort of early adopter treatment naive patients and are you doing anything to specifically target that population given that they're going to be the ones to sort of.

Jay Barth: Sure, thanks Anupam. I'll ask Jay Barth, our Chief Medical Officer, to handle that.

Jay Barth: Right now, we have the natural history data that we presented on approximately 14 patients. That'll continue to be the data set for now as we continue to expand that natural history data. That's a process that'll happen over time, so it's hard to pin down exactly when we'll have larger numbers on that. But from the natural history data that we have currently, there is a clear overlap between the ages of the patients in the treated cohort versus the natural history cohort. That's the basis of the comparison that we showed between the two, in which all 14 of the natural history patients declined at least two points on reversed, as opposed to just one of the eight treated patients over approximately two years, a clear differentiation. Great, thanks so much for taking the time. I'm sorry; I could also comment on the ages.

Likely sustained growth in the forward years.

Bradley Please sure yes, a couple of things. Thanks for the question. So you as a reminder, this is exactly the strategy that we outlined at launch which is focused on switch patients first they're already getting.

They are coming in every two weeks there infusions are getting reimbursed for fabry disease and Thats the pattern, we've seen in most markets.

And then in the sort of medium longer term start to see pickup in the diagnosed untreated patients certainly thats part of our strategy a couple of things remember outside the United States.

It really has to go through the physician population. So I think they're part of what you're seeing is as the physicians get more comfortable.

In treating their their patients there are more and more willing to put naive patients on there is also a phenomenon where you have family members. This is.

Excellent disease, who often have four or five diagnosed family members and so we're seeing more and more.

Jay Barth: That we would expect in any future natural history study.

Siblings, or lower parents and children coming onto their RFP as one family member has a positive experience. So I think theres definitely in this kind of organic growth going on there.

Jay Barth: There will be a broad range of ages, as we have now. The 14, the natural history data set that we have now covers a broad age range that's similar to the treated patients, and that will continue to be the case in the larger, expanded natural history data set.

And in the United States of course, you do have.

Different ability to educate patients and so we are doing what I think many others industry do in terms of having educational meetings with physicians and patients and I think thats a way to provide a more direct education. If you will.

Anupam Rama: But it will also include quite a number of younger children as well. Yeah, the whole range of younger children. Anupam, does that make sense?

And all of those things I think together and in particular I think the positive experience that we can infer from the high compliance and adherence rates.

Anupam Rama: Yep, great. Thanks so much for taking our questions. Thank you very much.

I think just gives the diagnosed and treated population of more and more confidence in coming onto Galafold.

Ritu Subhalaksmi Baral: Your next question comes from the line of Ritu Baral from Cohen. Your line is now open. Good morning, guys. Thanks for taking the question. Can I start with some of the marketing strategies for Gallifold? Now that your percentage of naive patients seems to be growing and picking up momentum, is there a profile of these sort of early adopter treatment naive patients? And are you doing anything to specifically target that population, given that they're going to be the ones to sort of likely sustain growth in the coming years?

Would it be.

As as you move forward are you targeting maybe patient groups more or sort of patient awareness campaigns or something like that I think in the United States were certainly doing that the.

Compliance and regulatory framework outside the us prevents you from going directly to patient groups with that kind of information, but in the US yes, we are.

Bradley L. Campbell: Bradley, please. Sure. Yeah, a couple of things. Thanks for the question. So, yeah, as a reminder, this is, you know, exactly the strategy that we outlined at launch, which is to focus on switch patients first. They're already getting – they're coming in every other week, they're infusions, they're already getting reimbursed for Fabry disease, and that's the pattern we've seen in most markets. And then, in the sort of medium, longer term, start to see pickup in diagnosed, untreated patients. Certainly, that's part of our strategy. A couple of things to remember.

And you had asked.

Rutu around are there specific kind of patient were targeting I mean look there there are what we've estimated in almost all of our major markets is there is a roughly equal number of diagnosed and treated patients. So very clearly there are patients out there who meet the treatment guidelines, who should be on treatment, who for whatever reason, we're choosing not to and we think that small molecule like galafold with the growing.

Body of evidence real world treatment evidence becomes more and more appealing to that population.

And just to add to that we think with this treatment naive population increasingly be an important part of the galafold adoption. It's in addition to that already diagnosed but untreated patients. It's also the newly diagnosed patients and also misdiagnosed patients people just discovering that they have fabry disease in there. We're beginning pilot studies to look into IBX clinics multiple sclerosis clinics, where you see high rates of misdiagnosis for what is actually February we believe.

Bradley L. Campbell: Outside the United States, it really has to go through the physician population. So I think there part of what you're seeing is as physicians get more comfortable treating their patients, they're more and more willing to put naive patients on. There is also a phenomenon where you have.

Bradley L. Campbell: You know, this is because it's an X-linked disease; you often have four or five diagnosed family members. And so we're seeing more and more, you know, siblings, or parents, and children coming into therapy as one family member has a positive experience. So I think there's definitely a kind of organic growth going on there.

So I think a lot more potential there and again in line with the product characteristics of Galafold.

Bradley L. Campbell: And in the United States, of course, you do have a different ability to educate patients. And so we're doing what I think many others in the industry do in terms of having educational meetings with physicians and patients. And I think that's a way to provide a more direct education, if you will. And all of those things, I think, together, and in particular, I think the positive experience that we can infer from the high compliance and adherence rates, I think just gives the diagnosed untreated population more and more confidence in coming onto Gallivold.

The high adherence compliance rates and the increasing awareness that fabry disease really is one of the largest human genetic disorders.

Super helpful.

And then.

So many questions I mean to be picky here.

Can you go over for a steep.

The statistics around that propel study.

Especially around superiority. He can you confirm that the comparison is.

If it's a baseline or.

Across arms and then what are your powering assumptions.

Ritu Subhalaksmi Baral: Would it be, as you move forward, are you targeting maybe patient groups more or sort of patient awareness campaigns or something like that?

Sure I am not sure what Weve disclosed publicly but I'll, let Jeff speak to that Jeff is in our gene therapy Center of Excellence in research Center down in Philadelphia with homes. So Jeff I'll, let you speak to why this study is so well powered.

Bradley L. Campbell: I think in the United States, we're certainly doing that; the compliance and regulatory framework outside the U.S. prevents you from going directly to patient groups with that kind of information, but in the U.S., yes, we are. Ritu around, are there a specific kind of patient we're targeting? I mean, look, there are what we've estimated in almost all of our major markets.

Sure. Thanks, John and Thanks for you for the question.

So the the power for propel is to have approximately 100 patient study. It is stratified by naive and switch and it's two to one stratification within naive and switch to pay TV a to standard of care ERP.

The powering assumptions were based on our phase one two study data on six minute walk in both switching nave patients.

Bradley L. Campbell: Please go to www.youtube.com or the link in the description below.

Where we looked at our effect that we had in our treated patients we compared that to what's been reported out in the medical literature for patients either starting on standard of care or treated longer term with standard of care, which should be comparable to the switch patients and based on that we came up with a set of assumptions. They gave us over 90% power to show superiority for TJ versus standard of care on six minute walk.

Bradley L. Campbell: And Rich, just to add to that, we think, you know, with this treatment-naive population increasingly being an important part of the Gallup Hold adoption, it's, you know, in addition to the already diagnosed but untreated patients, it's also the newly diagnosed patients and also misdiagnosed patients, people just discovering that they have a febrile disease, and there, you know, we're beginning pilot studies to look into IBS clinics So, you know, I think there is lots more potential there. And again, in line with the product characteristics of Gallup Hold, the high adherence compliance rates, and the increasing awareness that febrile disease really is one of the largest human genetic disorders.

So it's a cross arm comparison not compared to baseline.

Correct. So in a way it would be looking at each patient's changed from the time. They start the study to complete 12 months, but then you're actually comparing across treatments.

Got you are looking at the relevant change from start of treatment to end for each patient.

Got it.

And then sorry, one last very quick question for Daphne.

Definitely I think.

Hi, it's across all my rare disease companies I feel like you guys have been hit most by Forex and it might tie into the uptake.

That's very very robust uptake you guys have had in the UK and the pound and Brexit.

Ritu Subhalaksmi Baral: Super helpful. And then there were so many questions; I'm going to be picky here.

And your headquarters any impact that we should be thinking about through the end of the year.

Ritu Subhalaksmi Baral: Can you go over for us the statistics around the PROPEL study, especially around superiority? Can you confirm that the comparison is, if it's to baseline or across arms, and then what are your powering assumptions?

Okay, you actually know what's going on.

Well, yes, I mean foreign currencies are very hard to forecast and predict but we do have.

A very large percent of our revenue comes from Euro based and pound base.

Jeffrey P. Castelli: Sure. I'm not sure what we've disclosed publicly, but I'll let Jeff speak to that. Jeff is in our Gene Therapy Center of Excellence and Research Center down in Philadelphia with Hung. So, Jeff, I'll let you speak to why this study is so well-powered. Sure. Thanks, John, and thanks.

Transactions, so thats why we seem to be hit and as you said on a larger part with the foreign currency, we do have a natural hedge in the UK because our headquarters are there. So on a net basis. There is a natural hedge there we do have a larger exposure on the euro on a net basis.

But but again, it's it's really it's driven by the fact that a larger portion of our business right now is outside the U.S.

Jeffrey P. Castelli: and thanks Ritu for the question. So the Power for Propel, it's approximately a hundred patient study. It is stratified by Naive and Switch, and it's a two to one stratification within Naive and Switch, ATGAA to standard of care ERT. The powering assumptions were based on our phase one, two study data on six minute walks in both Switch and Naive patients, where we looked at the effect that we had in our treated patients. We compared that to what's been reported in the medical literature for patients starting on standard of care or treated longer term with standard of care, which would be comparable to the Switch patients. And based on that, we came up with a set of assumptions that gave us over 90% power to show superiority for ATGAA versus standard of care on a six minute walk.

And any potential business disruption with potential Brexit given the headquarters no weve already put our plans in place. So we are prepared for whichever eventuality Brexit ends up whether it's a smooth transition or that the hard Brexit. We are prepared yes. We spent a lot of time on that road too. So we're going to be in really good shape there.

Great. Thanks for taking all the questions.

Thank you.

Your next question comes from the line of thousand homes from Bank of America. Your line is now open.

I think that might be me good morning, guys sensing unfurnished narrative there yet.

Thanks for taking my questions.

Maybe John if we could follow up on propel again I know that you said in your prepared remarks that.

Jeffrey P. Castelli: So it's a cross-arm comparison, not compared. Correct. So, in a way, it would be looking at each patient's change from the time they start the study to complete 12 months, but then you're actually comparing across treatments. You're looking at the relevant change from start of treatment to end for each patient. And then, sorry, one last very quick question for Daphne. Daphne, I think across all of my rare disease companies, I feel like you guys have been hit hardest by 4X, and it might tie into the uptake, the very, very robust uptake you guys have had in the UK, the pound, and Brexit, and your headquarters. Any impact that we should be thinking about through the end of the year? You actually know what's going on. Well, yeah, I mean, foreign currencies are very hard to understand.

Enrollment is going well.

What.

Okay can you give us a sense of when that might come out.

That's question one question two is.

Santa Fe looks like they would be reading out their study their pivotal study for their follow ons limits on ahead of yours with that in mind. It seems like they are focusing more on lung function. So their primary endpoint. Although they are looking at six minute walk as a secondary what two doctors tell you about their preference for looking at lung function versus six minute walk.

And in the event that lets say set of being able to show statistical results for both lung function and six minute walk how do you think that would impact the perception physicians have about on Germany. Thanks.

Daphne E. Quimi: We do have a very large percent of our revenue coming from euro-based and pound-based transactions, so that's why we seem to be hit, as you said, by a larger part with foreign currency. We do have a natural hedge in the U.K. because our headquarters are there, so on a net P&L basis, there is a natural hedge there. We do have a larger exposure to the euro on a net P&L basis, but again, it's driven by the fact that a larger portion of our business right now is outside the U.S. And any potential business disruption with potential Brexit, given the headquarters? No. We've already put our plans in place, so we are prepared for whichever eventuality Brexit ends up being, whether it's a smooth transition or if it's a hard Brexit. We are prepared. Yeah,

Sure again, we've not done and not compared directly to that GA, what do they call. It Neo GA program that program is has been in development for for quite some time incentive fee.

The phase two results are known and I'll refer you to that we think our results certainly.

For for our drug compare quite favorably to what's known about standard of care or any other drug thats ever been in development, So with that said.

Jay I'll turn it to you for we spent a lot of time with the Kale wells in the World. We see again, a tremendous amount of excitement based around the phase two data that we've shown to date, it's quite distinct from any other program, including we believe that Sanofi program and development. So Jay do you want to comment on what the doctors say in terms of six minute walk versus.

Daphne E. Quimi: Yeah, we spent a lot of time on that RITU, so we're going to be in really good shape there.

Ritu Subhalaksmi Baral: Great. Thanks for taking all the questions. Thank you.

Daznim Ahams: Thank you.

John Crowley: Your next question comes from the line of Daznim Ahams from Bank of America. Your line is now open.

John Crowley: I think that might be me. Good morning, guys. Tazeen, I'm pretty sure it is you, yeah. Thanks for taking my questions. Maybe, John, we could follow up on Propel again. I know that you said in your prepared remarks that enrollment is going well.

FTC or other endpoints sure.

The.

As you said, John we have spent a lot of time with the clinical experts in the field.

In designing the propel study.

And they are very supportive of the primary endpoint is the six minute walk test as our regulators.

It's perfectly acceptable to them.

John Crowley: Once fully enrolled, can you give us a sense of when the app might come out? That's question one.

We had we have.

As shown very good data on the six minute walk test in our phase one two study so that.

John Crowley: Question two is, Sanofi looks like they would be reading out their study, their pivotal study for their follow-on to Lumizyme ahead of yours. With that in mind, it seems like they are focusing more on lung function for their primary endpoint, although they are looking at the six-minute walk as a secondary. What do doctors tell you about their preference for looking at lung function versus the six-minute walk? And in the event that, let's say, Sanofi is able to show statistical results for both lung function and the six-minute walk, how do you think that would impact the perception physicians have about undermined need? Thanks.

Support that as well.

For the six minute walk test is not just a measurement of walking ability of ambulation. It really is a comprehensive tests that includes pulmonary function cardiac function as well as skeletal muscle function. So we think it's a more comprehensive way of looking at the effect of the drug than merely SBC, which is a single element of pulmonary function testing of course, we aren't doing MPC as well that's expected by regulators.

And we're very comfortable with that as well based on our phase one two data, but looking at the whole picture below six minute walk test is.

Very good.

And for our purposes in the propel study the preferable primary endpoint.

John Crowley: Sure. Again, we've not done and not directly compared directly to that, what do they call it, the Neo-GAA program. That program has been in development for quite some time at Sanofi. You know, the Phase II results are known, and I'll refer you to that. We think our results certainly, you know, for our drug compare quite favorably to what's known about standard of care or any other drug that's ever been in development. So, with that said, Jay, I'll turn it to you. For, you know, we spent a lot of time with the key opinion leaders around the world. We see, again, a tremendous amount of excitement based around the Phase II data that we've shown to date that's quite distinct from any other program, including, we believe, that Sanofi program in development. So, Jay, do you want to comment on what the doctors say in terms of the six-minute walk versus FTC or other endpoints?

How do you feel about that.

Oh, sorry, I'm, sorry, no I didn't say again to remind everybody. We have a very very differentiated technology, which we think is a very distinct not only phase two clinical dataset, but all the preclinical work both at AMAK is ended the NIH. So.

We remain very very competent in our approach, but please go ahead I'm sorry.

No. Thanks for that I, just wanted to follow up and ask what your thoughts are without knowing the exact powering of how you're looking at everything would you at least expect.

Both six minute walk in lung function to move in the same direction, even if both of them may not be.

Physically significant.

Yes, Jay.

Generally speaking they do and we've seen that in a phase one two data.

And.

I think that we're looking for a directional similarity on the FCC.

Jay Barth: The

Supportive of the primary endpoint the six minute walk test.

Jay Barth: As you said, John, we have spent a lot of time with clinical experts in the field in designing the PROPEL study, and they are very supportive of the primary endpoint, the six-minute walk test, as are regulators. It's perfectly acceptable to them.

Okay, great. Thank you.

Great. Thank you.

Your next question comes from the line of Whitney Ijem from Guggenheim. Your line is now open.

Hey, guys. Good morning, Thanks for taking the question.

First one I guess, maybe on the on the pumping gene therapy side of it you know you alluded to progress a significant progress on that front I guess is the is there any color you can give us on on where you're headed either vector or modality or mode of delivery wise on in that program.

Jay Barth: We have shown very good data on the six-minute walk test in our Phase I-II study, so that supports that as well. The six-minute walk test is not just a measurement of walking ability but also of ambulation. It really is a comprehensive test that includes pulmonary function, cardiac function, as well as skeletal muscle function. So we think it's a more complete way of looking at the effect of the drug than merely FPC, which is a single element of pulmonary function testing. Of course, we are doing FPC as well. That's expected by regulators, and we're very comfortable with that as well based on our Phase I-II data. But looking at the whole picture, the six-minute walk test is very good, and for our purpose in the PROPEL study, the preferable primary test.

Sure. Thanks, Whitney maybe Jeff in Hong I'll, let you guys comment on what Weve developed with Dr. Wilson lab results, we've seen and again just reiterate that we expect to have all that completed in the second half of this year ready for the IB, enabling studies, so Jeff Tom Please.

Sure I'll start and then Hong will chime in so we reported earlier this year the Sgc T. Our first initial data from our pump paging therapy program.

Where were combining amick us design transgene that is really optimized for targeting targeting and cross correction and that novel Transgene was put into the views from Penn and we put that gene therapy into mice and showed.

Jay Barth: Again, to remind everybody, we have a very, very differentiated technology that we think is very distinct from not only the Phase II clinical data set, but all the preclinical work, both at Amicus and at the NIH. So we remain very, very confident in our approach, but please go ahead, I'm sorry.

Really quite remarkable glycogen reduction and all tissues, including in the spinal cord in the brain, which is really important to address and pumping in that study.

We delivered that gene therapy, just as an.

Hi, the injection into the mice.

John Crowley: No, thanks for that. I just wanted to follow up and ask what your thoughts are. Without knowing the exact powering of how you're looking at everything, would you at least expect both the six-minute walk and lung function to move in the same direction, even if both of them may not be statistically significant?

So we are really excited to progress our forward. We've said we are on track to have a clinical candidate.

Selected this year and then quickly move into IND, enabling studies.

So right now in terms of route of administration is likely to be systemic there is a chance we could add in a direct into the CSF.

Jay Barth: Yeah, Jay.

Jay Barth: Yeah.

Jay Barth: Generally speaking, they do, and we've seen that in our Phase I-II data. And I think that we're looking for directional similarity on the FEC as supportive of the primary endpoint, the six-minute walk test.

Administration as well.

We need to there's a chance we think we could adequacy target. The CNS also systemically. So thats one of the things we're still working out but we're really excited the progress to date on this approach of really designing the transgene for optimal cross correction and direct transduction with the pen technologies into all the key tissues as well so hum.

Jay Barth: Okay, great. Thank you. Great. Thank you.

Whitney Isham: Great, thank you.

Jeffrey P. Castelli: Your next question comes from the line of Whitney Isham from Guggenheim. Your line is now open. Hey guys, good morning.

Yes, the only thing I would add to that is on top of what Jeff has said is that we are working actively with Jims group at U. Penn to bleed developing a good process for manufacturing just material for both the R&D tough studies, but further for clinical supply.

Whitney Isham: Thanks for taking the questions. First one, I guess maybe on the Pompe gene therapy side, you alluded to progress, significant progress on that front, I guess. Is there any color you can give us on where you're headed either vector or modality or motive delivery wise in that program?

In the future.

Great and then second question for me is just on net savvy in Japan.

You alluded to the Jan da what needed to go in but did you talk about timelines around that and in terms of market opportunity there.

Jeffrey P. Castelli: Sure. Thanks, Whitney. Maybe Jeff and Hung, I'll let you guys comment on, you know, what we've developed with Dr. Wilson's lab, the results we've seen, and again, just reiterate that, you know, we expect to have all that completed in the second half of this year, ready for the IND-enabling study. So, Jeff, Hung, please.

Can you remind us how many patients there are and then third part of this one question is should we expect similar type deals.

Going forward as you kind of look to leverage your ex us commercialization capabilities. Thanks.

Sure Brendan you want to take them, yes sure. Thanks for the question, Yes, we're really excited here and I think from an overall timeline perspective, what we've said is the study is fully enrolled it's a 52 week study and so the next milestone really would be the J and the submission and we will provide an update on that when it goes in.

Jeffrey P. Castelli: Sure, I'll start and then Hung will chime in. So, earlier this year at ASGCT, we reported our first initial data from our Pompe gene therapy program, where we're combining an amicus-designed transgene that is really optimized for targeting and cross-correction. And that novel transgene was put into the AAVs from Penn, and we put that gene therapy into mice and showed really quite remarkable glycogen reduction in all tissues, including in the spinal cord and the brain, which is really important to address in Pompe. In that study, we delivered that gene therapy just as an IV injection into the mice. So, we are really excited to progress that forward. We've said we are on track to have a clinical candidate selected this year and then quickly move into IND-enabling studies.

But the good news is the study's enrollment so we're waiting to see data there just a little bit of an overview of MPS seven which is the indication from upsetting. It's one of the rarest MPS disorders. So it's only about 200 patients in the developed world who have been diagnosed.

And so it's a small population, but I think really when it reflects is.

Great acknowledgement of the team we have built in Japan.

The capabilities from a regulatory and commercial and clinical experience.

And also I think great a great combination between two to leading companies in the rare disease space and Ultragenyx and an amicable.

Jeffrey P. Castelli: So right now, in terms of the route of administration, it is likely to be systemic. There is a chance we could add in a direct route into the CSF administration as well, if we need to. There's a chance we think we could adequately target the CNS also systemically, so that's one of the things we're still working out. But we're really excited at the progress to date on this approach of really designing the transgene for optimal cross-correction and direct transduction with the PEN technologies into all the key tissues as well.

So I wouldn't expect to see.

More than very modest revenue from from this this product, but again, because we have the infrastructure in place, it's really purely leveraged on our side, which we think is great and again, it aligns very well with our mission and with Ultragenyx mission.

But we do to the last part of your question Winnie I do expect this to be an example of how amick is has built an infrastructure clinical commercial regulatory in Japan. We've got about 30 full time Anikas employees now in Japan.

Jeff Hung: And the only thing I would add to that, on top of what Jeff has said, is that we are actively working with...

To demonstrate to potential partners going forward that we may become a partner of choice in the rare diseases, where development into commercialization of products in Japan, and we'd expect a similar model to follow potentially in other geographies in the world.

Jeff Hung: Jim's group at UPenn to really develop a good process for manufacturing this material for both the IND tox studies but further for clinical supply in the future. Great

Whitney Isham: And then the second question for me is just on MEP-SEVI in Japan. You alluded to the JNDA, what needed to go in, but did you talk about timelines around that? And in terms of market opportunity there, can you remind us how many patients there are? And then the third part of this question is, should we expect similar-type deals going forward as you kind of look to leverage your ex-U.S. commercialization capabilities? Thanks

Great. Thank you operator.

Your next question comes from the line of Mike Olson from Baird. Your line is now open.

Hi, guys. Thanks for taking the question and congrats on all the progress as well.

I just had a question on Galafold, so you're starting expansion in Latin America with recent approval in Argentina, maybe you can just talk about your your broader plans in Latin America, and then secondly, when.

Bradley L. Campbell: Sure. Bradley, do you want to take this?

Bradley L. Campbell: Yeah, sure. Thanks, Wendy, for the question.

When you start to.

Bradley L. Campbell: Yeah, we're really excited here. You know, I think from an overall timeline perspective, what we've said is that the IAS study is fully enrolled. It's a 52-week study, and so the next milestone really would be the JNDA submission, and we'll provide an update on that when it goes in. But the good news is that the study's enrolled, and so we're waiting to see data there. So I wouldn't expect to see, you know, more than very modest revenue from this product, but again, because we have the infrastructure in place, it's really purely leveraged on our side, which we think is great.

Book revenues in that region. Thanks.

Yeah. So.

Thanks, Mike for the question Latin American as you know is it is a really large geographies important geography traditionally for the rare diseases.

For Fabry disease is an important part of our development program.

The regulatory ER infrastructure down there and timelines is changed in a number of the market. So I think it's taken a little bit longer there, we really see that as kind of a next year and years. After growth driver. We do have a handful of patients that we've mentioned before that are on a named patient sales in Latin America, and we continue to see that as a modest impact really I would see this as kind of the next year and beyond.

Bradley L. Campbell: What we do to the last part of your question, Whitney, I do expect this to be, you know, an example of how Amicus has built an infrastructure, clinical, commercial, and regulatory, in Japan. We've got about 30 full-time Amicus employees now in Japan to demonstrate to potential partners going forward that we may become a partner of choice in rare diseases for the development and or commercialization of products in Japan, and we'd expect, you know, a similar model to follow potentially in other geographies in the world. Great Thank you, Operator.

A growth driver for us and and its Argentina, Brazil, excuse me, Colombia, Chile, others. So there's a there's a number of markets. There that have good reimbursement in diagnosis rates for fabry disease. It's just a matter of going through the regulatory process, which we're now well underway.

Great. Thank you.

Thanks, Mike.

Your next question comes from the line of Mohit Bansal from Citigroup. Your line is now open.

Hi, guys. This is Keith on for Mike Thanks for taking our questions and congrats on the progress this quarter.

Operator: Your next question comes from the line of Mike Oles from Baird. Your line is now open. Hi guys, thanks for taking the question and congratulations on all the progress as well. I just had a question about Galafold. So you're starting expansion in Latin America with recent approval in Argentina. Maybe you can just talk about your broader plans in Latin America.

Just on the Galafold launch it looks like it's tracking really well ahead of expectations [noise].

Could you characterize the 24% of global market that you're capturing a just in terms of U.S. versus rest of world and then looking forward what are your thoughts on the balance of amenable patients.

I know you mentioned conversions, but in the medium term what are your expectations in terms of capturing worldwide market share and I just have one follow up thanks.

Bradley L. Campbell: Yeah, so thanks, Mike, for the question. Latin America, as you know, is really, obviously, it's a big geography. It's an important geography traditionally for rare diseases, for febrile diseases. It was an important part of our development program. The regulatory infrastructure down there in timelines has changed in a number of the markets, so I think it's taken a little bit longer there, but we really see that as kind of a next year and beyond growth driver. We do have a handful of patients that we've mentioned before that are on named patient sales in Latin America, and we would continue to see that as a modest impact, but really, I would see this as kind of a next year And it's Argentina, Brazil, Colombia, Chile, others, so there are a number of markets there that have good reimbursement and diagnosis rates for febrile disease. It's just a matter of going through the regulatory process, which we're now well underway.

Yeah. So.

For that global market share of 24% now obviously, our earlier launch countries you five et cetera have a higher market share today and the U.S. is a lower margin. That's really just a matter of timing from a launch perspective. We do however, you will see an acute breakout the revenue now between international U.S. and over time, we think.

That probably peaks out at about.

A third of revenue global revenue coming from the United States will run kind of mature phase, but but we will continue to grow to reach that distribution as the market the U.S. matures.

From a and then your second question was around the switch in 19 and naive dynamics is that right.

Yeah, that's right.

Yeah. So again, that's a really important.

Mike Oles: Great, thank you. Thanks, Mike.

Mark are for us commercial metric for us to follow we always focused on switch patients first because they were captive in the market they were coming in to see their physicians every other week already getting reimbursed, but we knew in every market we've looked and we see this big.

Mohit Bansal: Your next question comes from the line of Mohit Bansal from Citigroup. Your line is now open. Hi guys, this is Keith-An from MOHIT.

Bradley L. Campbell: Thanks for taking our questions and congratulations on the progress this quarter. Just on the Galliford launch, it looks like it's tracking really well ahead of expectations. Could you characterize the 24% of the global market that you're capturing just in terms of U.S. versus rest of the world? And then, looking forward, what are your thoughts on the balance of amenable patients? I know you mentioned conversions, but in the medium term, what are your expectations in terms of capturing worldwide market share?

Number really equal to the treated number of diagnosed and treated patients. So there is clearly demand in the market for more treatment options and we really see galafold is uniquely suited to meet that in similar ways that you know some of the oral products in and ask it really grown that market that treated market and engage as well. So lots of examples of where you see in the long term and oral entrance into an injectable space really growing the market. So yes, just as you alluded to we would say we would see in a kind of medium term in the next few years that that percentage of switching naive gets to about 50 50, and then really in the long term. Our vision is this product could really substantially grow the markets to the point, where the majority of patients might have been diagnosed and treated patients. Yeah. So it's kind of right on track with strategy and we'll keep following that as an important.

Bradley L. Campbell: And I just have one follow-up. Thanks. Yeah.

Bradley L. Campbell: Yeah, so for that global market share, 24% now, obviously, our earlier launch countries, EU5, et cetera, have a higher market share today, and the US has a lower market share. That's really just a matter of timing from a launch perspective.

Bradley L. Campbell: We do, however, as you'll see in the queue, break out the revenue now between international and US. That probably peaks out at about a third of revenue, global revenue, coming from the United States when we're in a kind of mature phase, but we'll continue to grow to reach that distribution as the market in the U.S. matures. And then your second question was about the switch and naive dynamics, is that right? Yeah, that's right.

Metric of our strategy and our success in the market.

Okay. That's helpful. And then just on the global compliance and adherence rate at 90% do you think that it's driven by disease severity and patient population.

Or do you or should we expect to drop off at a later time point as the launch gets going and then just one more on Navy seal.

And six the Ace ER child, who showed no evidence of disease stabilization was there no response at all or was it just not hitting a threshold.

Bradley L. Campbell: Yeah, so again, that's a really important marker for us, a commercial metric for us to follow. We always focused on switch patients first because they were captive in the market. They were coming in to see their physicians every other week and already getting reimbursed.

And how did the progression compared to natural history. Thanks.

Yeah, Brad take the Galafold question Huh.

Sure.

Yes, so from a galafold perspective, Im sorry, I, just I was paying attention sealed six money, though yes. Those are two very different questions. Sorry go ahead with the first one get them.

Bradley L. Campbell: But we knew that in every market we've looked at, we see this big number really equal to the number of diagnosed untreated patients. So there's clearly demand in the market for more treatment options, and we really see Gallup Holders uniquely suited to meet that. In similar ways that, you know, some of the oral products in MS have really grown that market, that treated market, and DAH as well. So lots of examples of where, in the long term, an oral entrance into an injectable space is really growing the market. So, yeah, just as you alluded to, we would say, we would see, you know, in the kind of medium term, the next few years, that that percentage of switch and naive gets to about 50-50.

Sorry about that I'm, just about the global compliance, yes, yes, yes gotcha.

So from a global compliance and to hear as you know.

What's driving that so first of all now were you know were multiple years on in Germany. For example from launch and we continue to sustain that that 90 plus percent compliance and adherence and on the one thing that's by no accident. We spent a lot of time in every market in making sure that physicians and patients understand the importance of adherence.

And we in every market has different rules around how you can support that in some cases, we have nurses in some cases its physician education in some cases like in the United States. We have a case management team that helps support that process, but we have a number of we have an app for example that helps patients remember to take their drug. So we have a number of strategies and tactics to help actively support that on the other hand, you have to infer that if after so many years in the market patients are staying on drug at over 90%. It has to reflect some level of satisfaction and experience on the part of physicians and patients. So yes, we'll continue to watch it it is higher than almost any other drug we've seen but but again, it's something we actively try to support so I would I would suspect that will continue going forward.

Bradley L. Campbell: And then really, in the long term, our vision is, you know, this product could really substantially grow the market to the point where the majority of patients might have been diagnosed untreated patients in the end. So it's kind of right on track with our strategy, and we'll keep following that as an important metric of our strategy and our success in the market.

Bradley L. Campbell: Okay, that's helpful. And then just on the global compliance and adherence rate of 90%. Do you think that it's driven by disease severity and patient population? Or do you, or should we expect to drop off later time and point as the launch gets going? And then just one more on AAV, CL, and six, the eighth child who showed no evidence of disease stabilization. Was there no response at all, or was it just not hitting a threshold? And how did their progression compare to natural history?

Jay do you want to take a bet child and they see a lunch program right the.

The oldest patient was treated.

Bradley L. Campbell: Thanks.

Bradley L. Campbell: Brad, take the gullible question.

Bradley L. Campbell: Sure. Yeah, so from a Gallup perspective, I'm sorry. I was paying attention to see if I could remind you that...

Actual history data that would allow us to do a matched comparison to this patient.

Bradley L. Campbell: Well, yeah, those are two very different questions. Sorry, but go ahead.

So in terms of whether there is any effect here or not really can say at this point, but it's something that we'll be able to do once we have.

Bradley L. Campbell: Sorry about that. Just about global compliance. Yeah, yeah, yeah.

More comprehensive natural history, and able to amass comparison even for that.

Bradley L. Campbell: Yeah, gotcha, sorry. So, from a global compliance point of view, it's, you know, what's driving that. So first of all, now we're, you know, multiple years on in Germany, for example, from launch, and we continue to sustain that 90 plus percent compliance and adherence. And on the one hand, that's by no accident; we spend a lot of time in every market making sure that physicians and patients understand the importance of adherence. And we in, you know, every market has different rules around how you can support that. In some cases, we have nurses, in some cases, it's physician education, in some cases, like in the United States, we have a case management team that helps support that process. But we have a number; we have an app, for example, that helps patients remember to take their drugs.

Oldest treated patients.

Okay, Great. That's very helpful. Thank you guys.

Your next question comes from the line of Debjit Chattopadhyay from H.C. Wainwright. Your line is now open.

Hey, good morning, and thank you for taking my questions.

So and maybe I can start off on the gene therapy side, given the collaboration with Dr. Wilson what are your thoughts on capsid engineering with respect to liver deducted gene therapy, especially centered around the doe's.

And how those might incorporate going forward.

Sure.

Debjit Thanks for the question Jeff.

Yes, so we're working closely with Jim and his team on all of their.

Avi that they've developed and as well as they are working on new ABS.

I would say, we're always interested in looking at new.

Bradley L. Campbell: So we have a number of strategies and tactics to help actively support that. On the other hand, you have to infer that if, after so many years on the market, patients are staying on the drug at over 90 percent, it has to reflect some level of satisfaction and experience on the part of physicians and patients. So yeah, we'll continue to watch it. It is higher than almost any other drug we've seen. But Again, it's something we actively try to support. So I would suspect that will continue going forward.

Either engineered or discovered a these.

Right now as we've articulated previously our approach is not necessarily just partying the liver.

We are looking to address live our cardiac muscle even into the CNS transduced cells, and then to use cross correction too.

Even further deliver the protein to all the cells and tissues, but for other programs on the line, we certainly could be interested in other eightys with different for our business.

So in your prepared remarks, you kind of said do you want to necessarily comment on any regulatory discussions, but with your upcoming well must have data on 80, G.A. if that exceeds expectations would you consider engaging the regulators, especially considering a pivotal study would be pretty much end or by the end of the year.

Bradley L. Campbell: Jay, do you want to take the eighth child in the ALM6 program?

Jay Barth: The oldest patient that was treated for 79 months did show a decline over the 24-month period, a two-point decline. As to say how that compares to natural history, we can't really say that at this point because we're still in the process of collecting more natural history data that would allow us to do a match comparison to this patient. So in terms of whether there is any effect here or not, I really can't say at this point, but it's something I will be able to do once we have more comprehensive natural history and are able to do a mass comparison even for that oldest treated patient.

John is that a question on Jay is going to take.

Okay.

Yes.

Yes.

<unk>.

Okay, Hey, operator, sorry, this is Jeff and hung in Philadelphia, I, just got a tax that the.

Advocacy group in Cranberry got disconnected.

Yes, I'm sorry for the delay, but they are dialing back to now give me one second.

Jay Barth: Okay, great. That's so helpful. Thank you, guys.

[noise].

[laughter].

Jay Barth: Okay, great. That's so helpful. Thank you guys. Your next question comes from the line of Debjit Chattopadhyay from H.C. Wainwright. Your line is now open. Hey, good morning, and thank you for taking my questions. So maybe I can start off on the gene therapy side. Given the collaboration with Dr. Wilson, what are your thoughts on capsid engineering with respect to liver-directed gene therapy, especially centered around the dose and how those might be incorporated going forward?

Hi, operator.

We are not looking at that.

Yeah, I don't know what happened there.

Are we this is John probably so I would never happened before we got disconnected. So we're back on the call sorry about that.

Hey, just sometimes it can you hear me.

Yeah, Dennis sorry about I don't know what happened.

No I didn't realize I'm going to be that disruptive.

[laughter] I'm pretty sure is Verizon not you.

Well as you can hear me now.

Well if you.

So it should do and should I repeat my question I'm not sure. If you got guys caught that we cut out after your question on capsid engineering that I turn it over to Jeff Castelli in Hong.

Debjit Chattopadhyay: Sure, Devjah, thanks for the question. Jeff Hung?

Jeffrey P. Castelli: Yeah, so we're working closely with Jim and his team on all of their AAVs that they've developed, as well as they are working on new AAVs. I would say we're always interested in looking at new, either engineered or discovered AAVs. But right now, as we've articulated previously, our approach is not necessarily just targeting the liver. We are looking to address liver, cardiac, muscle, and even the CNS, to transduce cells and then to use cross-correction to even further deliver the protein to all the cells in those tissues. So in your prepared remarks, you kind of said you wouldn't necessarily comment on any regulatory discussions, but with your upcoming well muscle data on ATGAA, if that exceeds expectations, would you consider engaging the regulators, especially considering a pivotal study would be pretty much underway by the end of the year? John, is that a question Jay's going to take?

Okay. So my next one was.

I kind of.

Pointed to your prepared comments that you wouldn't necessarily comment on any regulatory discussions, but given your upcoming WMS data on AG of that exceeded expectations and considering a study would be fully enrolled would you consider engaging the agency on on X on accelerating the BLE.

We as you know have breakthrough therapy designation, we are constantly in a very positive dialogue with the agency. The base case in any of the assumptions remains that we completed pivotal study for Pyl and that remains the basis for full approval in us and Europe .

John Crowley: [inaudible]

John Crowley: Okay, hey, hey operators, sorry, this is Jeff and Hung in Philadelphia. I just...

And.

Then any read throughs from the compelling seal and six update into sealant, three and thoughts on whether super physiologic expression could be detrimental and CNN three.

Operator: We just got a text that the Amicus group in Cranberry got disconnected.

Operator: Yes, I'm sorry for the delay, but they are dialing back now. Give me one second.

Yes, we think actually very positive read through for the Intrathecal platform that we have at AMAK is particularly into sealant three the largest of the baton diseases.

Operator: I operator. We are now connected. Yeah, I don't know what happened there. This is John Crowley. Sorry, it would never happen before we got disconnected. So we're back on the call. Sorry about that.

Hi, Jamie or Geoff do you guys want to comment on why we think is read through to seal and three and then while so we don't think there is a concern with any over expression.

John Crowley: Hey, this is Daljit. Can you hear me?

John Crowley: Sorry about that; I don't know what happened.

John Crowley: Alright, no worries. I didn't realize I was going to be that disruptive.

Sure Don or Darren. Please go ahead.

Yes, I would say on six and CLM three they are both different mutations, but both caused nurown a lysosomal dysfunction theyre both proteins that are within the cell.

John Crowley: I'm pretty sure it's Verizon, not you.

John Crowley: Well, at least you can hear me now. Should I repeat my question? I'm not sure if you guys got that.

So we think the read through is quite significant from sale on six to sale and three in terms of our ability to address a certain number of neurons both in the spinal cord and in the brain in sealing six and the and the benefits BC there that that should be directly transferable to sale and three.

John Crowley: Did we cut out after your question on capstan engineering that I turned over to Jeff Castelli and Hung?

Debjit Chattopadhyay: Okay, so my next one was, I kind of pointed to your prepared comments that you wouldn't necessarily comment on any regulatory discussions, but given your upcoming WMS data on ATGAA, if that exceeds expectations, and considering your study would be fully enrolled, would you consider engaging the agency in accelerating the BLA?

In terms of and also all of the information we've learned across safety manufacturing with our sale on six program is also transferable toward sale and three we have seen no evidence in any of our studies of any concerns around over expression of the target tranche Dean.

John Crowley: We, as you know, have breakthrough therapy designation. We are constantly in very positive dialogue with the agency. The base case for any of the assumptions remains that we complete the pivotal study for pill, and that remains the basis for full approval in the U.S. and Europe.

It's been reported in a few cases in gene therapy across the whole field, but by and large most of the concerns have been around the vector safety itself and we've seen a really good safety profile for our gene therapy to date.

John Crowley: And then, any read-throughs from the compelling CLN6 update into CLN3, and thoughts on whether superphysiologic expression could be detrimental in CLN3?

Appreciate it thank you very much.

John Crowley: Yeah, we think this is actually a very positive read-through for the AAV intrathecal platform that we have at Amicus, particularly into CLN3, the largest of the Batten's diseases. Jay or Jeff, do you guys want to comment on why we think there's a read-through to CLN3, and then why also we don't think there's a concern with any overexpression?

Your next question comes from the line of course that is clear.

From Cantor Fitzgerald. Your line is now open.

Hi, good morning, everyone and thanks for taking my question I just wanted to touch on the draft guidance that was published yesterday on for Brad disease. While this is just the draft version were there any surprises or notable items you picked up on as you're moving your preclinical gene therapy asset Howard. Thank you.

Jeffrey P. Castelli: I'll start, please go ahead. Yeah, so with CLN6 and CLN3, they are both different mutations, but both cause neuronal lysosomal dysfunction. They're both proteins that are within the cell. So we think the read-through is quite significant from CLN6 to CLN3 in terms of our ability to

Sure. Thanks, Kristen we did read that of course, I'll, let Jeff and Jane comment on that.

Jeffrey P. Castelli: address a certain number of neurons, both in the spinal cord and in the brain.

Jay I started Jeff please chime in really no surprises there, it's very consistent with the end of the strategy, Yes, we have.

Jeffrey P. Castelli: In terms of, and also all of the information we've learned across safety, manufacturing with our CLN6 program is also transferable to CLN3. We have seen no evidence in any of our studies of any concerns around overexpression of the target transgene. You know, it's been reported in a few cases in gene therapy across the whole field, but by and large, most of the, you know, most of the cases have been reported in the target transgene. You know, it's been reported in a few cases in gene therapy across the whole field, but by and large, most of the concerns have been around the AAV vector safety itself, and we've seen a really good safety profile for our gene therapy to date.

Carry forward in our February program, we see a lot of.

The types of approaches that we have taken.

And that we plan to take in our future gene therapy program in February so nothing there that really changes the direction that we have set for gene therapy program.

Yes, Jeff anything to add.

No perfectly summarized by doing all right.

Yes tells us Chris in it.

For February we're very excited about the potential for what we're developing for gene therapy, particularly for patients with non amenable mutations who their only option today are the enzyme replacement therapies, we think that could be a great potential opportunity to help people who are not eligible for galafold.

Debjit Chattopadhyay: I appreciate it. Thank you so much. Your next question comes from the line of Kristen Kluska from Kantor Fitzgerald. Your line is... Hi, good morning everyone, and thanks for taking my question. I just wanted to touch on the draft guidance that was published yesterday on febrile disease. While this is just the draft version, were there any surprises or notable items you picked up on as you were moving your preclinical gene therapy asset forward? Thank you.

But again, we do think for any product in development in February as we saw with Galafold given the nature of the disease and the approved therapies to date that it is certainly going to be a comprehensive approach toward approval.

Great. Thank you so much.

Thank you.

Your next question comes from the line of Selbin Arista from Goldman Sachs. Your line is still open.

Yes, hi.

Thank you for taking my question. This is an area of right on for Salveen I just had a question on the data that was released early on sale I'm sick.

Kristen Brianne Kluska: Sure, thanks Kristen. We did read that, of course. I'll let Jeff and Jay comment on that.

Jeffrey P. Castelli: Jeff, you know, please chime in. Really no surprises there, it's very consistent with the end of the strategies that we have carried forward in our FabRAE program. We see a lot of the types of approaches that we have taken and that we plan to take in our future gene therapy program in FabRAE, so nothing there that really changes the direction that we have set for our gene therapy program.

There it looks like the batteries in in acute patients there is a sort of.

Light to me.

In Hamburg toward the Ben goes down and I was wondering whether there is some biomarker or am I right. They said that.

Can't explain that phenomenon, where.

Jeffrey P. Castelli: Yeah, Jeff. Anything to add? No.

Jeffrey P. Castelli: Perfectly summarized. Thank you. Yeah, I'd tell this, Kristen, it's, you know, for FEBRE, we're very excited about the potential for what we're developing for gene therapy, particularly for patients with non-amenable mutations whose only option today is enzyme replacement therapy. We think that could be a great potential opportunity to help people who are not eligible for GALIFOLD. But again, we do think for any product in development in FEBRE, as we saw with GALIFOLD, given the nature of the disease and the approved therapies to date, that it is certainly going to be a comprehensive approach toward approval.

How do you guys think about it thank you.

The.

Right now there's a search for a biomarker zones thing because its a membrane around protein is no.

Obviously biomarker, yet, but it's something that we're.

Working on with others, who are in the field.

In terms of Amreit data it really MRI data were collected within the study is something that we are.

Collecting now ourselves to analyze that so I can't speak to that yet but in terms of the increase that you noticed in a couple of patients.

There is the possibility of an increase in score for some patients.

Kristen Brianne Kluska: Great! Thank you so much.

Salveen Jaswal Richter: Thank you.

Jay Barth: Your next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open. Yes, hi. Thank you for taking the time to answer the question. This is Mariana Brightman for Salveen. I actually had a question about the data that was released earlier on CLM6. It looks like in a few patients, there is a sort of slight increase in the Hamburg score that then goes down, and I was wondering whether there is some biomarker or MRI data that can explain that phenomenon, or what do you guys think about it?

Depending on what their baseline scores were there's also some variability in the test given the fact that it depends on patient effort.

Which may be slightly different from a certain business.

Other factors such as illnesses or recent seizures for example.

Overall, I think the way to look at the data is over several time points not at any one individual time point.

Jay Barth: Thank you.

And what we see over the.

Jay Barth: Right now, there's a search for a biomarker in Salin 6, uh, because it's a membrane-bound protein. There's no, uh, obvious biomarker yet, but it's something that we're, uh, working on with others who are in the field. In terms of MRI data, the MRI data were collected within the study. It was something that we are collecting now ourselves to analyze, so I can't speak to that yet. But in terms of the increase that you noticed in a couple of patients, there is the possibility of an increase in score for some patients, depending on what their baseline scores were. There is also some variability in the test, given the fact that it depends on patient effort, which may be slightly different at a certain visit based on other factors, such as illnesses or recent seizures, for example. Overall, I think the way to look at the data is over several time points, not at any one individual time point. And what we see across seven of the eight patients, at least is very consistent measurements of their Hamburg-Modern Language scores, either for the younger patients, really. [inaudible]

Seven of the patients lease is very consistent measurements of their Hamburg motor language scores either for the younger patients real.

Stability I think maintaining the same stores overtime.

For the patients that are a bit older with somewhat lower scores, having some change in the sport initially, but then stabilizing I think it's a pattern over a longer period of time that really is informative about the effect of the gene therapy treatment not any one measurement.

So hope that helps and that's how we look at it.

Got it thank you.

Thanks very much.

Our last question will come from June zone at Janney. Your line is now open.

Hi, Thank you Hey, good question and just a quick one taleo high level question on the gene therapy programs.

Jay Barth: not any one measurement. So I hope that helps, and that's how we look at it.

Apparently you have put together, a really broad portfolio and I wonder when.

Salveen Jaswal Richter: Got it. Thank you. Our last question will come from Yun Zong at Jenny. Your line is now open. Hi, thank you for taking the question. And just a quick one, probably a high-level question on the gene therapy programs. Apparently, you have put together a really broad portfolio, and I wonder when...

When you consider them for example.

Prioritize certain programs over others.

Would that be completely depending on the data or you will see kind of strategic consideration.

Thinking about them Youre product work programs outside the gene therapy portfolio. Thank you.

Yun Zong: Thank you.

John Crowley: Sure, thank you. I think, you know, with any of our programs, it'll be based on the strength of the data and the impact we think we could have for patients, given the platforms that we're developing, together with the unmet need in the patient community. I think those are the two most important factors. But we've built in a lot of capacity internally for R&D, leveraging what Dr. Wilson is doing, and leveraging what our partners at Nationwide and Sanford Health are doing to be able to put as many of these programs through preclinical development and, hopefully, into the clinic. Again, we're also expanding our partnerships in manufacturing for gene therapies as well as planning to build our own process science center of excellence and gene therapy manufacturing center of excellence. And we'll have more news on that in the months ahead as well. So we're making sure we have the full infrastructure together with all the capital, including the capital we've just raised, to be able to put as many of these programs forward into the clinic and, hopefully, through the clinic as possible. Great, thank you. Thank you.

Sure. Thank you I think you know with any of our programs. It will be based on the strength of the data and the impact. We think we can have for patients given the platforms that we are developing together with the unmet need in the patient community I think those are the two most important factors.

But weve done a lot of capacity internally R&D leveraging with Dr. Wilson is doing leveraging with our partners at nationwide and Sanford health are doing.

To be able to put as many of these programs through preclinical development and hopefully into the clinic and again, we're also expanding our partnerships in manufacturing for gene therapies as well as planning to build our own process Science Center of excellence in gene therapy manufacturing Center of excellence and will have more news on that in the months ahead as well. So we're making sure we have the full infrastructure together with all the capital.

Including the capital we've just raised to be able to put as many of these programs forward into the clinic and hopefully through the clinic as possible.

Great. Thank you.

Thank you.

Operator: At this time, I would now like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks.

At this time I would now like to turn the conference about on Mr. John Crowley.

Chairman and CEO for closing remarks.

John Crowley: Great, Operator, that's all we have today. Obviously, an excellent quarter for Galliford, for all the programs at Amicus, and quite a busy fall ahead of us into the second half of this year. Thank you, everybody, have a great day.

Great operator, that's all we have today and obviously an excellent quarter for Galafold for all the programs at AMAK is and quite a quite a busy.

Fall ahead of us into the second half.

This year. Thank you everybody have a great day.

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

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

Operator: BF-WATCH TV 2021