Q3 2020 Amicus Therapeutics Inc Earnings Call

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Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics third quarter 2020 financial results conference call and webcast.

Operator: Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics third quarter 2020 financial results conference call and webcast. At this time, all participants are in a listen-only mode.

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

Operator: 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. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Director of Investor Relations. You may begin. Thank you, friends. Good morning.

Third we will conduct a question and answer session and instructions will follow at that time.

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

As a reminder, this conference call is being recorded.

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

Mr. Andrew Fund, then director of Investor Relations.

You may begin.

Thank you Randy good morning, Thank you for joining our conference call to discuss amicus Therapeutics third quarter 2020 financial results and corporate highlights speaking on today's call. We have John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President Chief Operating Officer, Stefanie, Queenie, Chief Financial Officer, Dr., Jeff to Sally Chief Development Officer.

Andrew Faughnan: Thank you for joining our conference call to discuss Amicus Therapeutics' third quarter 2020 financial results and corporate highlights. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President and Chief Operating Officer, Daphne Quimi, Chief Financial Officer, Dr. Jeffrey Castelli, Chief Development Officer, and Dr. Mitch Goldman, Senior Vice President of Clinical Research. 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. 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 in 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.

Her docket, Mitch Goldman Senior Vice President of clinical research 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.

Our forward looking statements should not be regarded as representation 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 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.

Andrew Faughnan: 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 factors section of our annual report on Form 10-K for the year ended December 31, 2019, and the quarterly report on Form 10-Q for the quarter ended September 30, 2020, to be filed later today with the Securities and Exchange Commission. At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer John?

These 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 30, Onest 2019, and the quarterly report quarterly report on form 10-Q for the quarter ended September Thirtyth 2020 to be filed later today.

With the Securities and Exchange Commission.

At this time it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer Tom.

Great. Thank you Andrew and welcome everyone to <unk> third quarter 2020 results conference call as we did last quarter to quarter. We hope you and your families continue to remain safe and healthy.

John Crowley: Great. Thank you, Andrew, and welcome, everyone, to our third quarter 2020 results conference call. As we did last quarter, we hope you and your families continue to remain safe and healthy. Our leadership team at Amicus continues to emphasize a range of programs and initiatives to protect and support our global workforce during the ongoing pandemic.

Our leadership team at M.. It gets continues to emphasize or range of programs and initiatives.

Protect and support our global workforce during the ongoing pandemic.

John Crowley: While adapting to all of the changes brought about by the global pandemic, for Amicus, 2020 has been a period of excellent growth and execution across all aspects of our business, including science, clinical, regulatory, and, as you see, our commercial effort, as we continue to build one of the next great biotechnology companies, positioned and poised to impact people around the world living with rare diseases. As we did in this morning's press release, I'd like to highlight several key accomplishments. First... Galliford continues its strong launch performance and remains the cornerstone of our success. With $67.4 million in third quarter revenue, the Gallup Hold launch continues to exceed expectations.

While adapting to the role of between Jews brought about by the global pandemic. Ramic is 2020 has been a period of excellent growth and execution.

Across all aspects of our business, including same clinic.

Clinical regulatory and as you see our commercial effort as we continue to build whenever the next great biotechnology companies.

Positioned and poised to impact people around the world living with rare diseases.

As we did in this mornings press release I'd like to highlight several key accomplishment.

First.

Galafold continues its strong launch performance and remains the cornerstone of our success.

With $67.4 million in third quarter revenue.

California launch continues to exceed expectations.

John Crowley: The third quarter revenue represents the performance across all the global business, including new patient starts from both switch and naive patients throughout the quarter. Second, our key R&D timelines remain on track. We now expect the Phase III PROPEL study for ATGAA in late-onset Pompe disease to read out in the first quarter of 2021.

The third quarter revenue represents the performance across all the global business, including new patient starts from both switch and naive patients throughout the quarter.

Second our key R&D timelines remain on track.

We now expect the phase III propelled study.

For 80, GA in late onset pump a disease to.

To read out in the first quarter of Twentytwenty one.

John Crowley: Additionally, the rolling VLA submission remains on schedule, and we expect the first submission before the end of this year. Today, also, we'll be sharing results from the Amicus-sponsored natural history study in Pompe disease. Within our gene therapy pipeline, we continue to move forward our lead batten disease programs for both CLN6 and CLN3, as well as our most advanced preclinical gene therapy programs. Through our major research collaboration with Dr. Jim Wilson and the University of Pennsylvania, we are pleased to announce this morning that a Fabry disease gene therapy clinical candidate has now been selected to move into IND-enabling studies. Based on the data that we have seen to date, this program has moved much faster than originally planned and highlights the capabilities and potential that this collaboration can bring to people living with rare diseases. And third, following our strategic financing in the third quarter, Amicus' cash position is sufficient to achieve self-sustainability without the need for any future diluted financing.

Additionally, the rolling BLA submission remains on schedule and we expect the first submission before the end of this year.

Today also will be sharing results from the AMAK is sponsored natural history study in pump a disease.

Within our gene therapy pipeline, we continue to move forward, our lead batten disease programs for both seal and six and CLM Cree as well as our most advanced preclinical gene therapy programs.

Through our major research collaboration with Dr., Jim Wilson, and the University of Pennsylvania. We are pleased to announce this morning that a fabry disease gene therapy clinical candidate has now been selected to move into R&D, enabling studies.

Based on the data that we have seen to date. This program has moved much faster than originally planned for.

And highlights the capabilities and potential that this collaboration can bring to people living with rare diseases.

And third following our strategic financing in the third quarter. The amicus cash position is sufficient to achieve self sustainability without the need for any future dilutive financings.

John Crowley: Our continued revenue growth, our prudent expense management, and the growth potential for Amicus have allowed us to reach this important milestone as we continue to realize our vision of delivering groundbreaking, and we believe potentially curative new medicines for people living with rare diseases around the world. Turning to slide four, we are well on track to achieve our five key strategic priorities for 2020. These include Gallifold, our precision medicine for fever; we will continue to drive Gallifold to more people living with febrile disease with amenable variants in existing and new geographies. We look to achieve global product revenue of $250 million to $260 million this year.

Our continued revenue growth.

Our prudent expense management and the growth potential for Amick IHS has allowed us to reach this important milestone as we continued to realize our vision of delivering groundbreaking.

And we believe potentially curative new medicines for people living with rare diseases around the world.

Turning to slide four we are well on track to achieve our five key strategic priorities for Twentytwenty. These.

These include.

Galafold, our precision medicine for Fabry.

We will continue to drive galafold to more people living with fabry disease with amenable variance in existing and new geographies we.

We look to achieve global product revenue of 250 million to $260 million this year.

Two we are increasing the clinical regulatory menu.

Bradley L. Campbell: Here, we are increasing the clinical regulatory, manufacturing, and launch planning activities surrounding the Pompei program as we move this therapy toward approval. Finally, we are advancing our industry-leading rare disease gene therapy portfolio. Stemming from our new Global Research and Gene Therapy Center of Excellence in Philadelphia, we will continue to advance the clinical development, manufacturing, and regulatory discussions for both our CLN-6 and CLN-3 BATN programs. In addition, we are progressing our Pompe gene therapy towards IND and, for the first time, announced that an IND candidate has been declared for our February gene therapy program. A lot of work is underway with our manufacturing partners for the manufacture and scale up of the gene therapy potential IND candidate. And again, we will continue to maintain a strong financial position as we carefully manage our expenses and our investments. And we remain fully funded through all major milestones. So, with that introduction, let me now go ahead and hand the call over to Bradley Campbell, our president and chief operating officer, to further highlight Galliford's performance. Bradley

Manufacturing and launch planning activities surrounding the pump pay program as we move this therapy toward approval.

Three we are advancing our industry, leading rare disease gene therapy portfolio.

Stemming from our new Global research and Gene therapy Center of excellence in Philadelphia, We will continue to advance the clinical development manufacturing and regulatory discussions for both our CLM six and CLM three battery programs.

In addition, we are progressing our pumping gene therapy towards high end D and for the first time announced that an ideal candidate has been declared for our fabric gene therapy program.

A lot of work is underway and our manufacturing partners for the manufacturing scale up of the gene therapy potentially MD candidates.

And again, we will continue to maintain the strong financial position as we carefully manage our expenses and our investments and we remain fully funded through all major milestones. So with that introduction, let me now go head and hand, the call over to Bradley Campbell, our President and Chief operating officer to further.

Highlight the Galafold performance forever.

Bradley L. Campbell: Thanks, John. Good morning, everyone. As John mentioned, I'll walk you through in more detail our Gallup Hold performance for the quarter. And I'll start on slide six, where we go through the continued growth of Gallup Hold revenue in the third quarter of 2020. We give here our global snapshot of Gallup Hold's commercial progress, and for the third quarter, our total product revenue was $67.4 million, driven by strong patient demand, favorable reimbursement dynamics, and business continuity. Importantly, the global compliance and adherence rate continues to exceed 90%. The geographic breakdown of revenue during the quarter was $47.2 million, or 70% of the revenue generated outside of the United States, and the remaining $20.3 million, or 30%, coming from within the United States.

Thanks, John Good morning, everyone.

As John mentioned I'll walk you through in more detail, our galafold performance for the quarter.

I'll start on slide six where we go through the continued growth of Galafold revenue in the third quarter of 2020.

Bradley L. Campbell: And I'm pleased to announce today the addition of Poland, Iceland, Luxembourg, and Argentina to the growing list of countries around the world that have Regulatory Approvals, and now Access to Reimbursement. As a reminder, before these newest editions, we had approvals in 40 countries and commercial sales in over 30 of those today. This expanding global footprint is important not just to support the continued expansion of access to Galliford for Fabre patients, but it also lays a very strong foundation which is highly leverageable to support the potential launch of ATGAA and future products as well. Turning now to slide seven, as John mentioned, the third quarter was another strong quarter for us. The business continues to be incredibly resilient, and the quarter comes in above internal expectations for Gallup Gold, with patience added in all of our major geographies outside the United States. In select geographies outside the United States, we did see the COVID pandemic impacting the rate of new patient starts, largely due to disruptions in the interactions between patients and Importantly, though, our supply chain remains fully intact.

Supply chain remains fully and test our customers have confidence that they can access Gallup poll in our field team has been able to achieve a substantial majority of their pre covid touch points through a combination of in person digital telephonic and other means of interacting with their positions.

Bradley L. Campbell: Our customers have confidence that they can access Gallifold, and our field team has been able to achieve a substantial majority of their pre-COVID touch points through a combination of in-person, digital, telephonic, and other means of interacting with their physicians. Of course, as we close out the year, we will continue to monitor the pandemic's impact and duration. But the good news is today, with 10 months under our belts, we're confident we will deliver on our guidance and see continued growth into next year. From a numbers perspective, you can see that third-quarter sales increased 38% from third-quarter 2019, which does include a 3% benefit from foreign exchange. From a true operational performance perspective, sales increased by 35% compared to the same time last year.

Of course, as we close up a year, we will continue to monitor the pretense the pandemics impacts from duration, but the good news is today with 10 months under our belt. We're confident we will deliver on our guidance and see continued growth into next year.

From another perspective, you can see the third quarter sales increased 38% from third quarter of 2019, which does include 3% benefit from foreign exchange from a true operational performance perspective sales increased by 35% compared to at the same time last year, so great growth from from quarter 2019 to quarter of 2002.

Bradley L. Campbell: So great growth from quarter 2019 to quarter 2020. And on the left-hand side, we show our quarterly performance over the past several quarters. And as we mentioned in previous calls, while we do continue to expect strong quarter-to-quarter growth, due to a variety of factors, that growth is typically non-violent.

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And on the left hand side, we show our quarterly performance of the past several quarters and as we mentioned in previous calls while we do continue to expect strong quarter to quarter growth due to a variety of factors that growth is typically nonlinear.

Bradley L. Campbell: And again, despite the recent COVID-related headwinds and certain ex-US geographies, we continue to be very confident in our guidance of 250 to 260 million in full year global sales. And in fact, we can say at this time that we expect to come in at the top half of that. Turning to slide eight, with several years of performance behind us, we can confidently say we're on a path to that $500 million sales opportunity in 2023. As I outlined previously, to get to $500 million in global sales, we expect a five-year compound annual growth rate of about 40% from 2018 to 2023, and we expect to generate $1 billion in cumulative revenue between 2020 and 2022 alone, which, of course, goes a long way towards funding our R&D and operating expenses over that period.

And again, despite the recent cover the related headwinds in certain <unk> Geography's, we continue to be very confident in our guidance of $250 million to $260 million in full year global sales and in fact, we can say at this time that we expect to come in at the top half of that range.

Turning to slide eight with several years now performance behind US we can confidently say, we are on a path to that $500 million sales opportunity in 2023.

As about one previously to get to $500 million global sales, we expect a five year compound annual growth rate of about 40% from 2018 to 2023 and.

And we expect to generate $1 billion and cumulative revenue between 2020, and 2022 alone which of course goes a long way towards funding, our R&D and operating expenses over that period.

Mitch Goldman: We've also gained even further confidence in the $1 billion revenue opportunity to peak as we continue to see significant growth in the FabRay market globally, driven by continued diagnosis from high-risk screening, newborn screening, and other diagnostic initiatives, which we're also investing in. And we have work in exclusivity in the U.S. and Europe, in addition to our multiple Orange Book-listed patents that give us IP coverage into the late 2030s. So a lot of opportunities to continue to provide access to Gallup Hold globally for a long period. So with that review of the revenue performance for the year, let me continue now to hand the call over to Dr. Mitch Goldman, who's our Senior Vice President of Clinical Research, to highlight our ATGAA program. Mitch.

We've also gained even further confidence in the 1 billion dollar revenue opportunity to peek and we continue to see significant growth in the fabric market globally, driven by continued diagnosis from high risk screening newborn screening and other diagnostic initiatives, which we're also investing in.

And we have working exclusivity in the U S and Europe. In addition to our multiple on forklifts patents that give us IP coverage into the late twenties thirties. So a lot of opportunity to continue to provide access to gallop hold globally for a long period to come.

Mitch Goldman: Thank you, Brad. Good morning, everyone. Moving on to our R&D updates on slide 10, we want to remind everyone of our highly differentiated Pompe therapy, ATGAA, and its mechanism of action. ATGAA is our novel next-generation therapy consisting of ATP-200 or glucosidase alpha, an investigational human-recombinant GAA enzyme administered into the body through intravenous infusion designed to target muscle cells throughout the body, combined with AT2221 or micro The AT2221 is administered shortly before the infusion of the Enzyme Replacement Therapy begins and is intended to bind and stabilize the ATB200 in circulation, allowing more active enzymes to be taken up into cells and delivered to life. The combination of enzyme replacement therapy and enzyme stabilizer is one major distinction from the standard of care and from any treatment currently in development for Pompeii. The other distinction, and a more impactful advancement, is the unique carbohydrate profile of the enzyme cell.

Mitch Goldman: Dr. Hung Do, our Chief Science Officer, and his team have been working over the past decade to develop this POMPEI enzyme replacement therapy that has both improved binding to heart receptors for efficient uptake into cells, as well as the ability to be processed by those cells in the mature form of GAA. Today here, we're showing the natural history data from the Amicus POM-002 study in people living with late-onset Pompe disease, treated long-term with the current standard of care.

After is for efficient uptake into cells as well as the ability to be processed by those cells to the mature form.

[music].

So with that in mind will turn to the next slide slide 11 today here, we are showing the natural history data and the 'cause palm or two study in people living with late onset pump agencies trigger.

Treated with long term trends long term that the current standard of care ALS leukocytes Alpha.

The palm oil to study data shown on the left hand of the slide compared to the medical literature on the right hand side.

Mitch Goldman: The POM-002 study data shown on the left hand of the slide is compared to the medical literature on the right hand side. These POM-02 data are consistent with the medical literature, reproducing it, where patients on average generally see a benefit on six-minute walk tests over the first year or two on treatment, which then stabilizes, but over time, declines. These data support the need for new therapies and underpin the design assumptions for Propel. Next slide, please. Importantly, shown on this slide is that our timelines remain on track with data expected from Propel in the first quarter of 2021. To date, more than 97 percent of the 3100 planned infusions and assessments for the ongoing Propel studies have been completed on schedule.

Jeffrey P. Castelli: In addition, we continue to enroll patients in the Pediatric Studies and advance our manufacturing platform to support a 2021 BLA and MAA filing. We want to express our thanks to all the Pompeii Clinical City participants, their families, to all our investigators and site staff, and to our cross-functional Amicus Pompeii team for the collective, unwavering commitment and supportive efforts during this unprecedented time. With that, let me hand the call over to Dr. Jeff Castelli, the Chief Development Officer, to review our portfolio of gene therapies.

Jeffrey P. Castelli: Thank you, Mitch, and good morning, everyone. Moving now to slide 14, I'll briefly highlight here our industry-leading portfolio of gene therapies for rare diseases. During this time of COVID, we've been able to maintain our critical science and lead programs across the gene therapy portfolio, including CLN6 and CLN3 Batten disease, as well as the Pompei and Fabry gene therapy programs at Penn, starting with our Batten disease franchise on slide 15. Last month at the Virtual Child Neurology Society Annual Meeting, we reported positive interim data in our ongoing Phase I-II clinical study in CLN6-BA The data demonstrated a meaningful effect in slowing disease progression out to 24 months compared to natural history. The data continues to suggest that our gene therapy has the potential to be a treatment option for children living with CLN6, an ultra-rare debilitating condition that leads to progressive declines in cognitive and motor function and often results in death in early childhood. We continue to advance regulatory discussions to finalize the clinical and regulatory path and expect to provide an update in 2021 for CLN6. We believe the initial CLN6 results also provide important read-through for our clinical study in CLN3 batten, the most common form of childhood neurodegeneration.

I'll need we've been able to maintain heart critical science and lead programs across the gene therapy portfolio, including ceiling, six and seven three baton disease as well as a pompeii and fabry gene therapy programs at 10.

Starting with our battens disease franchise on slide 15 <unk>.

Last month that the virtual child Neurology Society annual meeting you've reported positive interim data and our ongoing phase one two clinical study and ceiling six bad movies.

The data demonstrated a meaningful effect and slowing disease progression after 24 months compared to natural history.

The data continues to suggest that are gene therapy has the potential there'll be a treatment option for children living with C. O N six pattern and ultra rare debilitating condition that leads to progressive declines in cognitive and motor function and often results in depth in early childhood.

We continued to advance regulatory discussions to finalize the clinical and regulatory path and expect to provide an update in 2021 for sale and six.

We believe the initial ceiling six results also provide important read through for a clinical study in C. O N. Three battens disease. The most common form of childhood in order to generation. We plan to report the initial data from the ongoing phase one to study in C. O N. Three early next year at a medical conference.

Jeffrey P. Castelli: We plan to report initial data from the ongoing Phase 1-2 study in CLN3 early next year at a medical conference. Additionally, we continue to make great progress in our commercial manufacturing process for both CLN6 and CLN3 programs and remain on track to initiate studies for these programs next year using this commercial material. Moving on to slide 16, I would like to remind you of the research collaboration between Amicus and the University of Pennsylvania, which will be an important driver of growth in the future. This collaboration with the Wilson Lab at Penn combines Amicus' protein engineering and glycobiology expertise with Penn's gene transfer technologies and expertise to develop novel gene therapies designed for optimal cellular uptake, targeting, stability, dosing, safety, and manufacturability.

Additionally, we continue to make great progress in our commercial manufacturing process for both ceiling six and see on three programs remain on track to initiate studies for these programs next year using this commercial material.

Moving on to slide 16, I would like to remind you of the research collaboration between Amicas in the University of Pennsylvania, which would be an important driver of growth in the future.

This collaboration with the Wilson lab at Penn combines Amicas is protein engineering and Glycobiarsol G expertise with pens, Jean transfer technologies and expertise to develop novel gene therapies designed for optimal cellular uptake targeting stability dosing safety and manufacturer Bill.

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As part of this collaborations Amicas has rights to 50 plus diseases, including five currently inactive preclinical programs.

Jeffrey P. Castelli: As part of this collaboration, Amicus has rights to 50-plus diseases, including five currently in active preclinical programs. Moving on to slide 17, as part of that collaboration, we are very pleased to announce that a gene therapy clinical IND candidate has been selected for Fabry Disease. Initial data from our proprietary AAV gene therapy, which includes a ubiquitous promoter and an amicus-engineered GLA transgene, demonstrated significantly better GL3 reduction and knockout mites than one containing the wild-type GLA transgene.

Moving on to slide 17, as part of that collaboration.

Very pleased to announce that a gene therapy clinical I N D candidate has been selected.

For February disease.

Jeffrey P. Castelli: We're very excited to now show that in addition to engineering transgenes for improved protein uptake into target cells, as we did for our Pompeii IND-AAD gene therapy candidate, we're also able now to engineer transgenes for improved stability and activity. We will have the full set of preclinical data for this Fabry-Jean therapy presented at a medical conference in early 2021. We're very excited about this initial data in Fabry and continue to make progress across our preclinical gene therapy programs, as highlighted by the takeaways here on slide 18. With that, I would like to now turn the call over to Daphne Quimi to review our financial results, guidance, and outlook. Daphne?

Daphne E. Quimi: Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 20 with our income statement for the quarter ending September 30th, 2020. For the third quarter, we achieved Galliford revenue of $67.4 million, which is a 38% increase over the third quarter of 2019. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 35%, further benefited by a positive currency impact of 3%. Cost of goods sold as a percentage of net sales was 12.5% in the third quarter as compared to 11.5% for the prior year period.

Daphne E. Quimi: The increase in cost of goods sold as a percent of revenue was due to sales in select countries achieving the highest royalty rate in this quarter. Total operating expenses were $111.8 million in the third quarter of 2020, reflecting an increase as compared to $100.5 million in the third quarter of 2019. On a non-GAAP basis, total operating expenses were $92.4 million in the third quarter of 2020 as compared to $89.7 million in the third quarter of 2019. The increase in research and development costs reflected our continued investment to support the gene therapy program pipeline and the PROPEL study, as well as realignment with our strategic priorities. Our investment in research and development includes the impact of the implementation of cost-reduction measures, as does the decrease in selling, general, and administrative expenses. We define non-GAAP operating expenses as research and development and SG&A expenses, excluding share-based compensation, changes in fair value of contingent consideration, and depreciation. The net loss for the third quarter was $64 million, or $0.25 per share, as compared to a net loss of $61.8 million, or $0.24 per share, for the prior year period.

And depreciation.

Net loss for the third quarter was $64 million or 25 cents per share as compared to net loss of $61.8 million or 24 cents per share for the prior year period.

As of September Thirtyth 2020, we had approximately 260 million shares outstanding.

Turning now to slide 21, following our $400 million senior secured term loan facility. We are now on a clear path to self sustainability without the need for any future dilutive financing.

We have achieved this milestone by our continued revenue growth with galafold as well as driving efficiencies cost savings and careful expense management.

Daphne E. Quimi: As of September 30, 2020, we had approximately 260 million shares outstanding. Turning now to slide 21, following our $400 million Senior Secured Term Loan Facility, we are now on a clear path to self-sustainability without the need for any future diluted financing. We have achieved this milestone through our continued revenue growth with Gallup Hold, as well as driving efficiencies, cost savings, and careful expense management. Securing this financing with market-setting terms gives us a strong financial platform to advance both patient and Amicus shareholder interests. Going forward, again to emphasize, we expect total non-GAAP operating expenses in 2020 to remain relatively flat from 2019 as we leverage the commercial, Global Commercial Infrastructure that is already in place for the ATGAA launch and other products in our pipeline. Additionally, we transition the costs associated with the development of ATGAA to multiple gene therapy programs in our pipeline. And we maintain financial discipline while meeting our objectives.

Daphne E. Quimi: To reiterate, all high-priority research programs in gene therapy are moving ahead on schedule, especially CLN3, CLN6, CLN7, CLN8, CLN9, CLN10, CLN11, CLN12, CLN13, CLN14, CLN15, CLN16, Pompei and Fabre, and we continue to fully support the work with the Wilson Lab at Penn. A few comments about our cash position and 2020 financial guidance. Cash, cash equivalents, and marketable securities were $509.1 million at September 30, 2020, compared to $452.7 million at December 31, 2019.

Daphne E. Quimi: We are reaffirming our full-year Galliford revenue guidance of $250 million to $260 million in addition to our non-GAAP operating expense guidance of $410 million to $420 million. And with that, I will turn the call back over to John for our closing. Great. Thanks, Daphne. So, as everybody can see, we have continued to be relentlessly focused on performance across the business. I'm incredibly proud of our team and the resilience that they've shown despite this great global pandemic and all the challenges brought about by it.

John Crowley: We have a great global team of passionate entrepreneurs who have led and will continue to lead us through this. And I am confident that as the world emerges from this crisis, Amicus will emerge even stronger. So, with that, operator, we're happy to take questions. Thank you. Ladies and gentlemen, if you have questions, please press star, then the number one on your touch screen.

Operator: At this time, we ask that you only ask one question. If you have any additional questions, please enter back into the queue. If your question has been answered, or you wish to remove yourself from the queue, please press the pound.

Yeah sure Bradley do you want to provide some more color there too on upon his question.

Yeah. Thanks on a bomb so you know it's.

Operator: Your first question comes from the line of Anupam Rama from JPMorgan. Your line is open. Hey guys, thanks so much for taking the question. Sure, Anupam, good morning. Hey, how are you, John?

It's still mix I mean, we have Japan in the U.S., who are still pretty early in their sort of launch cycle.

And so you're getting really strong switching in those markets. Although we are starting to see some nice patients come on there as well.

In Europe, It's really you know those are those are a little bit further along in their launch curve. So there you're seeing both switch and naive patients coming in on an almost an equal rate, which is what we what would we expect over the course of the evolution of the launch there and then maybe a third of the growth is is kind of new patients from.

John Crowley: Just a quick one from me. Thinking about slide seven in particular on Galliford, when you look deeper into the operational growth that you're seeing, how do we think about sort of deeper penetration into the core regions versus, say, new patient ads in some of the newer emerging market regions? Thanks so much.

Bradley L. Campbell: Yeah, sure, Bradley, do you want to provide some more color there to Anupam's question? Yeah, thanks, Anupam. So, you know, it's still mixed. I mean, we have Japan and the US who are still pretty early in their sort of launch cycle. And so you're getting really strong switching in those markets, although we are starting to see some naive patients come on there as well. In Europe, it's really, you know, those are those are a little bit further along in their launch curve. So there you're seeing both switch and naive patients coming on at almost an equal rate, which is what we would expect over the course of the evolution of the launch there. And then, you know, maybe a third of the growth is kind of new patients from different geographies. I highlighted a few on the call today. You know, none of those, in and of themselves, are large, particularly large markets.

Bradley L. Campbell: But when taken together, they're an important part of the growth story as well. So it is still a mix. And I think we're, you know, for the next two to three years, we're going to be very much in that kind of continue to penetrate the mature markets, continue to push the launch and the big new ones, Japan and the US, but also bring out as many of the small and mid-sized countries as we can. Great, thanks for taking our questions. Thanks, Samba.

Okay. That's a three new G. A study that we saw and and if you could just just one housekeeping stay on propel if you could talk about like the number of primary employee visits you've managed to retain and timing of that.

John Crowley: Thank you. Your next question comes from the line of Ritu Baral from Cowen. Your lines are open.

John Crowley: Good morning, guys. Thanks for taking the time to answer the question. Glad to hear you guys are doing well. I want to focus on, I say, slide 11, the new, sorry, the Pompei-POM-002 natural history data. I wanted to know how much the 002 data contributed to the powering of the POPEL study, first of all, and second, how do your potential assumptions around powering for POPEL change or not change if you think about the placebo arm of the Neo-GAA, the Phase III Neo-GAA study that we saw?

Good <unk>, okay. So <unk> curiously been taking notes I think that's only three questions. So that's actually quite good.

One question [laughter], but multiple part so yeah, we're happy to answer so let me before I ask Jeff and it's two way and again I'll just emphasize the Palm O O. Two study was originally done has the potential for a compare it to a hit there've been a window for and it really filing.

Here once we completed it I think it adds to our body of knowledge adds to the field, but it looks to be entirely consistent with everything that's been known about any benefit for <unk> and then the.

John Crowley: And if you could just, just one housekeeping thing on POPEL, if you could talk about, like, the number of primary endpoint visits you've managed to retain and the timing. Okay. So, Ritu, I've furiously been taking notes. I think that's only three questions, but that's actually quite good. One question. In multiple parts.

Decline over time, so with that Jeff and maybe you want to begin and then we can ask Mitch to add any comments or colors to it did you capture those questions from her to Jeff.

Jeff here on mute.

John Crowley: So, yeah, we're happy to answer. So, let me, before I ask Jeff and Mitch to weigh in again, I'll just emphasize that the POM-002 study was originally done as the potential for a comparator had there been a window for an early filing. Here, once we've completed it, I think it adds to our body of knowledge, adds to the field, but it looks to be entirely consistent with everything that's been known about any benefit for lumizyme and then the, you know, decline over time. So, with that, Jeff, and maybe you want to begin, and then we can ask Mitch to add any comments or colors to it. Did you capture those questions from Ritu, Jeff? I'm on mute.

No we still still can't hear you Jeff.

[laughter].

Give us one second route to sure we I have them open on video muted with our video system. So I can see you're trying to talk but.

Then we will go ahead, and and Mitch and I'll be happy to take your questions. So.

Mitch do you want to heal.

Talk about the first card in terms of cowering and what we assumed it I think takeaway is entirely consistent with all the assumptions. We had made required to seeing any of this data, but it did partly inform building a plan. So Mitchell, let you talk about the power.

I think it's real.

Largely right.

You know it helped us.

John Crowley: No, we still can't hear you, Jeff. Give us one second, Ritu. Sure. I have them up on video, muted with our video system, so I can see you trying to talk, but

Have a health datasets with the variability that we would see we use that along with our faith Tuesday.

John Crowley: You know what? Then we'll go ahead, and Mitch and I will be happy to take the questions. So, Mitch, do you want to talk about the first part in terms of powering and what we assumed? I think the takeaway is that it's entirely consistent with all the assumptions we had made prior to seeing any of this data, but it did partly inform building the plan. So, Mitch, I'll let you talk about the powering.

To really.

Understand moving against a six minute walk time point the variability in the in the.

In the variable in size. This study so that's how we landed on 100 or so patients to propel studying looking to deliver.

Deliver 15 to 20 meter improvement in six minute walk at the end of the study versus the the competitor L-glucose holidays.

No. Thank you minutes I think with this does and looking at all or two once we saw this is just gave US further confirmation then the study propel was extremely willpower.

Mitch Goldman: Sure, I think that's really largely right, John. I mean, it helped us have an in-house data set with the variability that we would see. We used that along with our phase two data to really understand moving against a six-minute walk time point, the variability in the Variable and Adder sides of the study.

And again based on what we know we think we need somewhere around 15, or so 15 to 20 meters delta to share with statistical significance on the superiority.

It's interesting to your second part of the question you referenced the D O data and.

Mitch Goldman: So that's how we landed on a hundred or so patients in the Propel study looking to deliver a 15 to 20 meter improvement in the six minute walk at the end of the study versus the Albuquerque siders. You know, it's interesting, Ritu, your second part of the question, you referenced the NEO data, and while I won't speak to the NEO arm, just their control arm, we did see that they had, I believe it was, a three-meter improvement at one year, so essentially flat to where those patients began. So if, for whatever reason, the patients randomized to lumizyme in the control arm of our study in the Propel study were to be closer to what we saw in NEO, it would just add to the power of our study as well. The third part of your question was, yeah, of course. And then the third part of your question was around assessments lately. You know, we did see some disruptions in the March-April timeframe. By mid to late May, all of the sites were receiving patients.

Speak to the D O arm just their control arm, we did see that they had I believe it was a three meter improvement that one year, so essentially flat to wear those patients began.

That is worse than we assumed for Lumens I'm again that is in the nineties patient population again, our study is about 70% switch how 'bout, 30% naive click with respect to the patient.

Our studies, we expected that they would look more like 25 or so meters was our assumption to live for whatever reason the patients randomized to loom as I'm in the control arm of our studying to propel study or to be closer to what we saw in D. O. It would just further add to the powering of our study as well.

The third part of your body or you know of.

Course, and then the third part of your question where around the assessments lately.

We did see some disruptions in the March April timeframe by mid to late May all of the sites will receiving patient patience, we're getting not only their infusions, but their assessments and again even in the the height of the pandemic back in the early spring the vast majority of patients we were seeing we're still getting there.

Mitch Goldman: Patients were getting not only their infusions but their assessments. And again, even in the height of the pandemic back in the early spring, the vast majority of patients we saw were still getting their infusions and all of their assessments. And when we look at the aggregate of the 3,100 assessments and infusions, we're still well more than 97% of those have gone off as planned. So the integrity of this study remains very high. And again, in any study, of course, you plan for misinfusions, misassessments, and we're actually in a better place than we assumed we would be without a pandemic. So, and I think that's a real testament to the effort of the team here.

Fusions and all of their assessments and we look at the aggregate of the 3100 assessments in infusions, we're still well more than 97% of those have gone office plan. So the integrity of this study remains very high.

Again in any study you play any study of course, you plan for missed infusions missed assessments and we're actually even with the pandemic. We're in a better place that we assumed we would be without a pandemic. So and I think that's a real testament to the effort of the team here.

Great and are you guys, making any adjustments for an increase in the pandemic correlated logistics uhm as cases arising right now than before.

Mitch Goldman: Great. And are you guys making any adjustments for an increase in pandemic-related logistics as cases are rising right now and before? We follow every patient every week. We've got a master tracker of every set of activities for every patient.

We follow every patient every week or get a mask [laughter] a master tracker of every set of activities for every patient and again the vast majority of patients now have completed that propels study.

Mitch Goldman: And again, the vast majority of patients now have completed the Propel study. You know, we of course remain blinded to all of that, but virtually all patients have completed it. The last patient out is scheduled in December. Perfect. Thank you so much.

Of course remained blinded to all of that but virtually all patients have completed last patient out is in scheduled in December.

Perfect. Thank you so much thanks for killing all the questions. Thank you it too of course.

John Crowley: Thanks for handling all the questions. Thank you, Ritu. Of course. Thank you. Your next question comes from the line of Joseph Schwartz, from SVB Learning. Go ahead.

Thank you. Your next question comes from the line Joseph Schwartz from S V be nearing go ahead.

John Crowley: Hi, I'm Juvie dialing in for Joe. Thanks for taking our question. My question is on APTAA. Could you just remind us if there are any key steps remaining to complete your rolling BLA submission once you have your phase 3 data? Sure, we will have completed and submitted by the end of this quarter the first module, the preclinical module; all of those activities have been completed, so that will begin the rolling VLA process, Julie. We are nearly complete with all of the PPQ activities.

John Crowley: We've completed the manufacturing parts of it, both the upstream and the downstream, so some final finishing work and time on the stability studies, and, of course, all the final reports necessary for that CMC module. And we're already drafting the clinical module, and once we have the ProPEL data, we'd expect to update the clinical module with all of that important data. So, no, there are no barriers left for us other than receiving the ProPEL data. Okay, great. Thank you. I'll hop back in the queue.

John Crowley: Great. Thank you, Jillian. Thank you. Next, we have Salveen Richter from Goldman Sachs. Good morning.

John Crowley: Thanks for taking my question. So, really, two around the gene therapy portfolio and one around your Fabre candidate that's moving forward and how you see it differentiated versus competitors out there. I think we've had a few others kind of discuss their target as well, or the protein as well as construct and approach here. And then, on the BATN program, what do you need to understand regulatory-wise in order to move forward or expand into the pit bull stage? Great, thanks, Salveen.

Initiated versus competitors out there I think we've had a few others kind of discuss their target as well or that the protein as well as construct and approach here and then on the Bachelor programs, what do you need to understand regulatory wise in order to move forward or expand into a pivotal.

Dave.

Great thing Sylvain hung maybe you can speak to the science work that went into our Fabry gene therapy and the differentiation what was unique about the protein and and the tech that you took and then.

John Crowley: Hung, maybe you can speak to the science work that went into our Fabry-Gene therapy and the differentiation. What was unique about the protein and the tech that you took? And then we can come to Salveen's baton's question in a moment, but go ahead, Hung, please.

Then we can come to sell these buttons question in a moment lets go ahead. Please.

Jeff Hung: Sure. Thanks, John. Hi Salveen.

Jeff Hung: Yes, to your question about how we developed our approach for the FibroAgene therapy, it actually is quite differentiated between us and how everyone else is approaching it. First and foremost, I think I should stress the importance of that protein. It's expressed as a dimer of two identical subunits, and it's imperative that that dimer stays together and intact for it to be functional.

Jeff Hung: And so with that in mind, what we've been able to do is engineer the transfer. So it produces a protein that maintains that dimer formation, and it maintains its activity throughout. And that's important, as shown in that middle panel or slide, that it remains active while it's secreted into the blood prior to its targeting to the various tissues. And so that is a huge advantage that we have seen where we've been able to increase the activity and potency, essentially, of that protein so that when it actually targets the specific cells, it is able to be much more potent and effective for clearing the substrate. So again, as far as we know, this is the only gene therapy approach that has made a more potent enzyme through transmission.

Jeff Hung: And then, Salveen, I'll just comment briefly on your questions around regulatory. Again, this year, we've spent an enormous amount of time and effort focused on the CNC and the technical operations parts of these programs. We've successfully completed the tech transfer from Nationwide Children's to Thermo Fisher Brammer. They are now producing at commercial scale, what we believe will be at commercial quality.

We've spent an enormous amount of time and effort focused on the CMC and the technical operations parts of these programs. We've successfully completed the tech transfer from nation My children to thermal Fisher Brammer. They are now producing at commercial will be believe will be the commercial scale and commercial quality.

John Crowley: A lot of work has gone into the analytical development, the tightening of the potency assay, and all the related analytics. So, in terms of regulatory interactions, a good part of our regulatory interactions are to make sure that the key regulatory bodies are comfortable with all of the technical operations and CNC components of both CLN6 and CLN3. And then, on the clinical side, as you know, we're going to dose additional patients in both of those diseases with commercial scale and quality material from Thermo Fisher. And right now, we're going to work with the regulators to figure out what is the right amount of time for additional follow-up for these patients. For CLN6, in particular, what is the amount of time?

A lot of work has gone into the analytical development that tightening of the potency assay and all the related analytics.

So in terms of regulatory interactions a good part of our regulatory interactions are to make sure that the key regulatory bodies are comfortable with all of the technical operations in CMC components of both CNN six N C. L. N. Three and then on the clinical side as you know we're going to dose additional patients in both of those diseases.

With the commercial scale and quality material from thermal Fisher.

And right now we're going to work with the regulators to figure out what.

What is the right amount of time for additional follow up for these patients.

John Crowley: And then, the number of patients as well. For CLN3, we've only dosed four patients with the Nationwide material. And to Jeff's point earlier, we'll be able to provide the first look at that clinical data in the early part of 2021. So we're very much looking forward to that. And then with the regulators, we know we need to move into a pivotal study there, and our guess is that'll be somewhere around two dozen or so patients in CLN3. And again, CLN3 is the largest of the Batten diseases and among the largest of the genetic fatal brain diseases in children. So, significant numbers of children suffering with that just horrible disease.

John Crowley: So we're moving as fast as we possibly can in those programs and in other programs, neurological Batten programs that continue through our preclinical pipeline. So lots more ahead on those programs in the next couple of quarters. Thank you. Your next question comes from the line of Mohit Bansal from SIPI. Your line is now open.

John Crowley: Hey there, this is Keith Hahn from MOHIT. Thanks for taking our questions and congratulations on the quarter. So, we're just looking at expectations for gene therapy in general. They seem to have moved away from a cure and more towards sort of a very long-term therapeutic. It's obviously very early, but looking at the CLN6 data, the probability of no decline seems to be pushed out rather than avoided entirely.

John Crowley: How are you thinking about the mid- and long-term expectations for this therapy, and then what would be the bar there for efficacy over time? Thanks. Yeah, candidly, we continue to have very high expectations. You know, these Batten's disease programs, as you know, Keith, are really just awful, devastating diseases. And it seems that the earlier that you treat children in their disease progression, the better the outcome will be. Right now, it's unclear whether you can ever reverse neurodegeneration. It doesn't seem that you can, based on today's tools and technologies.

Overtime. Thanks, Yeah candidly, we continue to have very high expectations.

These batten disease programs as you know Q.

They're really just awful devastating diseases and it seems that the earlier that you treat children in the or in their disease progression the better the outcome will be.

John Crowley: So it's really important to identify these children as soon as you can after birth and to administer gene therapy. But we remain optimistic that for children without significant brain damage, with a properly targeted and safe gene therapy, you can make a profound difference in fundamentally changing their quality of life. Will it be a cure for some of the younger children, or something more in the lines of a curative therapy? We still think potentially so, but, you know, much to be seen over time. All right. Mitch, Jeff, if you guys want to add color. Hey, John, this is Jeff. Can you hear me? You're back. Yeah, you paid your phone bill.

Jeffrey P. Castelli: Yeah, my apologies for getting disconnected at the wrong time the previous time. One thing I will comment on, you know, as John mentioned, we really think it's the baseline severity that can impact whether kids treated with these neurological gene therapies can remain largely normal and live a pretty normal life, so close to what you would call a cure, versus if they're impacted already and there's other damage that's done, there still can be some progression that's not really due to the underlying genetic factor that you' So we think that that's a big factor here. In terms of durability of gene therapies, we know that's an issue with some of the liver-directed gene therapies and some of the blood disorders, for example.

Jeffrey P. Castelli: With CNS delivery, we really do expect that these gene therapies should be durable. There's really not a lot of data suggesting that there's any sort of turning off of expressing cells or turnover, so we are really hopeful that durability, at least for CNS-directed gene therapies, could be quite good. Thank you. Thank you. The next one would be from... Go ahead, Operator. I'm sorry.

CNS directed gene therapies could be could be quite good.

Thank you the next one would be from.

Going up or I'm sorry.

Jeffrey P. Castelli: Thank you, sir. The next one will be from Mike Olds from Baird, Elizabeth. Hey guys, thanks for taking the questions. Good morning.

Thank you Sir.

Next will be from Mike Olson from from Baird. Your line is open.

Hey, guys. Thanks for taking the time, Mike Good morning.

Morning, just a quick follow up on the propel study a John you mentioned, you'll kind of get the last patient through in December.

John Crowley: Just a quick follow-up on the PROPEL study, John. You mentioned you'll kind of get the last patient through in December. So maybe you can talk a little bit about the timeframe to sort of turn that data set around and provide the top line results. And I'm just curious if you see any unique challenges created by COVID and if that could potentially extend the timelines there. Thanks. Thanks, Mike. Yeah, again, we've tightened the timeline. We've always said it would be in the first half of 2021.

John Crowley: Now that we're just on the cusp of the last patient out, we're confident that we'll be able to report the data out in the first quarter. You know, that patient will receive the last infusion assessment as part of the protocol in December. At that point, shortly thereafter, into early 2021, you'll lock the database, and we'll go through all of our protocols that we have in place and standard operating procedures for our clinical operations, clinical research teams to go through all of the data once we're confident of the integrity of the data and the databases scrubbing all of that. We don't foresee anything with respect to COVID that would delay that, but we'll have to And that's why I think we gave ourselves some cushion by narrowing it to Q1.

John Crowley: But we're also very confident that, you know, in the 12 weeks or so of Q1, that should be ample time, even if there are some challenges at some sites and in the final data assembly. So, I think we'll be in a really good place to report that out in Q1. And again, by Q2, we expect to file the VLA in the United States and complete that submission. Thank you. The next will be from Evan Wong from Guggenheim Security. Yolanda M G O D F I T S O H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M H O M

Thank you the next will be from.

Evan Wang from Guggenheim Securities Your.

Your line is open.

Hi, Thanks for taking the question I had a question on Jan gene therapy, CMC broadly and I always seem some difficulty with is communication or respect to the guidelines.

John Crowley: I had a question on gene therapy, CMC, broadly. You know, we've seen some difficulty with, I guess, communication or with respect to the guidelines with FDA, with comparability, especially between clinical grade and commercial grade. You know, has there been any change with respect to, you know, regulatory agency requirements with respect to CMC? Or is this some sort of growing thing for just the gene therapy industry? and its impact, you know, works towards building out in-house capabilities compared to utilizing a CMO.

Let's compare ability, especially between clinical grade the commercial grade has or has there been any change the stricter regulatory agency requirements with respect to CMC or.

Or is it sort of some sort of growing pains bridge to the gene therapy industry.

And as it does impact work towards building out in house capabilities compared to utilizing a CMO. Thanks.

John Crowley: Yeah, you know, Evan, I'll just state broadly, I think if Amicus is going to become one of the world's leading gene therapy companies, we've also got to be one of the world's leading gene therapy companies in process science. In many respects, in gene therapy, the process is the product. So we have been just hyper focused on it. And again, I think actually Amicus is uniquely suited to succeed here, based on all the experience we have had with ATGAA.

Yes, and I'll just state broadly I think and I guess, it's going to become one of the worlds leading gene therapy companies. We've also got to be one of the worlds leading gene therapy companies in process science in many respects in gene therapy. The process is the product. So we have been just hyper focused on it and again I think actually advocates is.

John Crowley: You know, that is among the most complicated glycosylated biologics ever produced. And for that Pompei enzyme therapy program, we have successfully scaled it and produced it at commercial scale with our partners at WUSHI Biologics. We have a really sophisticated and experienced team in technical operations, in quality, in regulatory CMC. And we're applying all of that excellence together with our partners at Thermo Fisher Brammer in these lead batten programs, but then also with other CMOs with Jim Wilson and his UPenn team. So a lot of work on the CMC, the analytics, and manufacturing side. I actually think it'll be a great strategic advantage for Amicus.

John Crowley: To the part of your question about the regulatory environment, without question, in the last 12 to 18 months, the regulatory framework at the FDA has continued to evolve. There have been much strengthened and much heightened standards around the analytical components, CMC requirements, and manufacturing requirements for gene therapy. And I actually think that's a good thing.

John Crowley: I think it's necessary. I think it's important for patient safety, but also important so that we understand exactly what we're providing the patient so we can assess efficacy as well. You know, again, gene therapy is fundamentally different. With AAVs in particular, most patients are going to, at least based on today's technologies, have one shot. And we've got one shot as innovators and drug developers to get it right for patients. So that's why we are just hyper-focused and putting a lot of focused attention, a lot of our resources into the CMC side. We are busy at work designing a world-class, state-of-the-art clinical manufacturing gene therapy facility, and we're also in the early stages of thinking through a larger commercial facility as well. We would expect in very early 2021 that we'll be able to describe a lot of that more fully.

Claire.

Most patients are going to at least based on today's technologies have one shot.

And we've got one shot as innovators in drug developers to get it right for patients. So thats why we are just hyper focused on a lot of focus attention a lot of our resources into the CMC side.

We are.

Is the at work designing a world class state of the art.

Cynical manufacturing gene therapy facility and we're also in the early stages of thinking through a larger commercial scale facility as well we would expect in very early 2021 that we'll be able to describe a lot of that more fully so a lot of work behind the scenes on on CMC.

John Crowley: So, a lot of work behind the scenes on CMC for all of our programs, really, including investigating next-generation technologies and working to develop and invent, I think, some of the key technologies in gene therapy manufacturing. So, we really, really want to be, and we need to be at the forefront of gene therapy manufacturing. Thank you. Your next question comes from the line of Kristen Klusky from Cantor Fitzgerald.

John Crowley: Please go ahead. Hi everyone. Thanks for taking my questions and congrats on the great progress you've made over the last quarter. So I wanted to ask about Fabry disease, how are you looking at the trends of identifying more amenable mutations on the label in the U.S. and Europe? And then for your gene therapy program, could you remind us what you would view as the key differentiators and advantages of Amicus versus some of your peers, including your understanding of the market, of course, through Galliford? And I know in the past that you discussed in detail the importance of a really safe approach here, as well as targeting higher transduction to the heart and other key organs. Great. Thanks, Kristen.

Bradley L. Campbell: Nice to hear from you. Bradley, do you want to take the first part about identifying more patients who may be suitable for Gallifold? Sure, yeah, so I think there's really two pieces to that. One of them, Kristen, as I'm sure you saw last quarter, we did announce that we expanded the European label to include all of the potential mutations of the GALI gene. So we went from sort of 350 or so mutations in the European label to 1,384 mutations in the European label. And we were able to do that through the great internal science team that we have. And with the really creative approach that the Europeans took with the ability to update that label, again, just with the preclinical assay determining amenability.

Stations of the European label to 1384 mutations in the European label, and we were able to do that for the great internal science team that we have.

And with the really creative approach that the Europeans took with the ability to update that label again, just with the preclinical assay determining amenability in the United States that process is a little bit different there. We actually have to have a patient who has been diagnosed with a new mutation in order to update the labels.

Bradley L. Campbell: In the United States, that process is a little bit different. There, we actually have to have a patient who has been diagnosed with a new mutation in order to update the label. So you see that the number is growing in the United States, but it's growing in kind of ones and twos as we find patients with those mutations. So that's one piece of the puzzle.

So you see that the number is growing in the United States, but it's it's growing and kind of ones and twos as we find patients with those mutations. So that's one piece of the puzzle I think the other pieces is identifying new fabric patient there were doing a ton of work we've talked before about some of the interesting data looking at an Underdiagnosed February disease.

Bradley L. Campbell: I think the other piece is identifying new Fab-Ray patients. And there, we're doing a ton of work. We've talked before about some of the interesting data looking at underdiagnosed Fab-Ray disease in MS clinics. And we're going through some investigator-initiated studies to look more closely at that. We've also looked at pain and GI clinics.

M S clinics, and we're going through some some investigator initiated studies to look more closely at that we've also looked at pain and Gi clinics.

Bradley L. Campbell: And we're doing some really exciting things around artificial intelligence, looking at improving the diagnostics. And we hope maybe in the first part of next year, we can talk a little bit more about some of the exciting findings there. And then, of course, all the newborn screening initiatives going on in the United States and around the world.

And we're doing some really exciting things around both artificial intelligence looking at improving the diagnostics and we hope maybe the first part of next year, we could talk a little bit more about some of the exciting finding there.

And then of course, all the newborn screening initiatives going on in the United States and around the World and then finally, we've talked about the work we've done with that come to call them to be K, which of course helps.

Bradley L. Campbell: And then, finally, we talked about the work we did with a company called Invitae, which, of course, helps promote the use of diagnostic genetic testing. And there, we partnered with them to include Fab-Ray in the panel, and in particular, Fab-Ray with amenable mutations in the panel that they use. And then, the last piece of the puzzle, I guess, is that for every Fab-Ray patient we find, because it's an X-linked disease, you typically find four to five family members with undiagnosed Fab-Ray as well. So there is a ton of work going on there.

Promote the use of diagnostic genetic testing and there we partner with them to include that Brian in the panel and in particular amenable separate that with the mental mutations and.

And the panel to pay you. So and then the last piece of the puzzle I guess is that for every February patient would be fine because it's an excellent disease you typically find.

Four to five family members with an diagnose February as well so a ton of work going on there I think everybody in the field is really focused on that and I think that's why you continue to see significant increases a diagnosis broadly and also identifying more patience with a medical mutations.

Bradley L. Campbell: I think everybody in the field is really focused on that, and I think that's why you continue to see significant increases in diagnosis broadly and also in identifying more patients with amenable mutations. Thanks, Bradley. Jeff, maybe you and Hung want to go ahead and tackle the gene therapy question. I think it's a very high-level reminder of what we're doing and how it complements what Jim Wilson is doing. You know, Hung, you provided an excellent explanation for Salveen's question specific to Sebre, but I think Kristen's question is a bit more thinking holistically about the overall approach to gene therapy and, again, why this is going to continue to be such an important part of the Amicus business in the future Sure, John, maybe I'll start, Hung, and then you can add in. Please, yeah.

Thanks, Bradley, except maybe few and hung want to go ahead and tackle the chemotherapy question I think he was very high level again, a reminder of what we're doing Howard compliments with your Wilson is feeling like no Hunter provided an excellent explanation for sell these questions specific around.

Separate but any Christian Christmas question is a bit more thinking holistically about the overall approach and chemotherapy and again why this is going to continue to be such an important part the amicas business ahead.

Sure John maybe I'll start hung and then you can add in Louisiana.

I do think that obviously, our experienced with Galliford in February on development and.

Jeffrey P. Castelli: And I do think that, you know, obviously our experience with Galliford and Febree development; interaction with that community over the years has helped us a lot in our gene therapy efforts and that profile that we're looking for. We've learned about the importance of stabilized proteins, not just for our chaperoning and Gallifle, but also we know that you can combine chaperones with ERTs for stability to help improve those proteins. So really, when you look at the market, we do think gallifered patients have a pretty high burden to switch to gene therapy. We do think, obviously, in patients that are on ERT that don't have the option of an oral molecule, clearly there's an opportunity for a convenient one-time therapy. But safety is definitely very important in terms of gene therapy because there are existing treatments that do address a lot of issues in Fabry disease today.

Interaction with that community over the years has helped US a lot on our gene therapy and that profile that were looking for.

We've learned about the importance of us of stabilized proteins not just for our chaperoning in Gallup poll, but also we know that you can combine chaperones with the parties for stability to help improve those proteins.

So really when you look at the market. We do think Calicle patients has a pretty high burden to switch to a gene therapy. We do think obviously in patients that are on ear T that don't have an option of an oral molecule clearly there's an opportunity for a convenient one time therapy, but safety is definitely very.

And in terms of the gene therapy, because there are existing treatments that to address a lot of the.

Issues in February disease today, so when we looked at our gene therapy. There is the main approaches out there either targeting a specific oregon like deliver directed approaches or the cardio trophic approaches, but no matter what what's clear is given that February multi systemic and you need to address kidney heart.

Jeffrey P. Castelli: So when we look at gene therapy, you know, there are the main approaches out there, either targeting a specific organ, like the liver-directed approaches or the cardiotropic approaches. But no matter what, what's clear is given that Fabry is multisystemic, and you need to address kidney, heart, skin, and vasculature, you need to have some main element of cross correction where you get some transduction in some cells, but those cells are going to need to also secrete the protein into the blood. And that is going to need to travel to other cells. And we've really focused on optimizing that cross-correction through this stabilized transgene. So when that enzyme gets put out into the blood, it's now very stable at a neutral pH. As it gets into cells and tissues, it stays very active.

Skin.

Last glitch or you need to have some main element of cross correction, where you get some transduction and some cells, but those cells are going to need to also secrete the protein into the blood and that is gonna need to then travel to other cells and tissues and treat them and we've really focused on.

Optimizing that cross correction.

Through the stabilized transgene, so when that.

Enzyme gets put out into the blood. It's now very stable at the neutral ph if it gets into cells and tissues. It stays very active and in essence, we've made a more potent gene therapy. We believe so with whatever small amounts of that enzyme that does get put out into the blood that it will have optimal efficacy. So you don't need to go to doses that start to have safety concerns.

Jeffrey P. Castelli: And in essence, we've made a more potent gene therapy, we believe. So with whatever small amount of that enzyme that does get put out into the blood, it will have optimal efficacy, and we don't need to go to doses that start to have safety concerns. So we think we have learned a lot about the approach here and really are excited about this stabilized construct. Hung, anything to add?

<unk>.

So we think we have learned a lot about the approach here and really are excited about this stabilized construct for improving cross correction.

Hung anything to add.

Yeah, just one last thing I would add on this from <unk> excellent explanation. There I think just from a practical the appointment do two eight is that we are very cognizant E.

Jeff Hung: It's just one last thing I would add from Jeff's explanation. I think from a practical point of view, too, that we are very cognizant of the transduction efficiency between preclinical studies and ultimately in people. We know that in primates, and particularly in humans, the transduction efficiency goes way down. And so with that in mind, what we are trying to develop is a very potent protein so that when the efficiency drops when dosing humans, we are certain that we are actually able to achieve the level of enzyme produced, and that's going to be effective. So again, all of these factors are ways in terms of how we are developing this approach, which we believe is quite differentiated and which we hope to be quite improved over the current methodology.

<unk> transduction efficiency between pre.

Preclinical studies gaming ultimately people, we know that the.

In primates, and particularly in humans transcription efficiency goes way down and so with that in mind, what we're trying to develop it's a very potent protein. So that you know.

The efficiency drops.

Dosing humans, we are certain that we were actually you'll be able to achieve the level of enzyme produce and that's gonna be effective. So again all of these factors kind of our.

Or wait in terms of how we are developing <unk> approach, which we believe is quite differentiable and we hope to be quite improved over a.

The current methodologies right now.

Jeff Hung: Great, thank you guys. Thank you. You have your next question from Ritu Baral from Cowen. Please go ahead.

Great. Thank you guys.

Thank you you have your next question from redo Brown from common. Please go ahead.

Hi, guys. Thanks for taking a follow up and Jeff No running away at this time like right now.

Jeffrey P. Castelli: Hi guys, thanks for taking the follow-up. And Jeff, no running away this time.

Black on back on that one 517, when you're talking about the fabric gene therapy Uhm could you guys give a little more clarity on that second bullet proprietary a cascade.

Jeffrey P. Castelli: My question is on, back on slide 17, when you're talking about the Fabry gene therapy, could you guys give a little more clarity on that second bullet, the proprietary AUD capsid? Can you talk about how you're thinking about these proprietary capsids, both for Fabry and for Pompe, given what we've seen with safety in the D&D studies around complement activation, the potential liver issues seen with the XLMTM program, and when we might get a little more clarity on what they are. Truly Procrite.

Can you talk about how you're thinking about these proprietary perhaps is that for February.

And for Pompeii, given given what we see.

With safety.

In the <unk> studies or a couple of an explanation the potential liver issue scene with the excellent PM program and when we might get a little more clarity on what what makes <unk>.

Truly proprietary.

Jeffrey P. Castelli: I'm not sure Hung would want to speak to these, or Jeff, but yeah. I'll start, I guess, John, and then Hung, please chime in, so Ritu, I hope you can hear me this time. I'm not avoiding you. So, you know, the proprietary capsids are coming from our collaborators at UPenn. We were well aware of the various safety concerns that have risen up in the gene therapy AAV field broadly on, you know, the high systemic dosing, some of the challenges with liver damage or DRG toxicity. You know, these capsids, we think, would still likely have those safety concerns. You know, generally, it seems like this is a broad AAV effect and not necessarily specific to one specific type of AAV. I know some people try to point to, well, it might be this specific AAV9 or this specific AAV8 or this approach that's causing this toxicity. We think it's a little more broad. It could be a little, could be impacted by manufacturing processes, and maybe the capsids and transgenes have slight differences.

Sure a hot or maybe to the free jazz yeah.

I'll I'll start I guess, China and Hong please triangle.

Hope you can hear me this time I'm not avoiding you.

So the proprietary copses are coming from our collaborators that U Penn.

We were well aware of the various safety concerns that have risen up into gene therapy Avi filled broadly on the highest systemic dosing some of the challenges on liver damage or deogee toxicity. These.

These caps that we think would still likely have that.

Those concerns generally it seems like these are abroad, AAV effect and not necessarily specific to one specific type of Avi I know some people try to 0.20 it might be the specific avi nine or the specific aviate or this approach is causing this toxicity. We think it's a little more broad it could be a little could be in.

Packet by manufacturing processes, and maybe the cops and trashing some slight differences, but overall.

Jeff Hung: But overall, we're trying to address some of those concerns by having very potent transgenes and proteins, so we don't need to push on the dose. [inaudible] the common clades of AAVs, but we'll provide those specifics when we can, but we're really addressing the main concerns through having a potent trans. Hung, anything to add to that? And just one last point here is that, you know, Jeff, you kind of touched on this earlier, that the capsid that we're using actually has pretty broad transduction efficiency, and so we're not reliant on any one specific organ or tissue. And so we think that having broad transduction allows for the expression and secretion of this protein so that we can get much more effective cross-correction.

We're trying to address some of those concerns by having very potent trans genes and proteins. So we don't need to push on the dose we can keep in a safe level. There's also technologies that are that are covers appendant working on to help produce things like the arg toxicity and we have early access to those types of technology.

<unk> through the collaboration as well so.

In terms of the captured itself there were not yet disclosing what it is it is.

One of the common cleaves of Aav's, but.

We will provide those specifics when we can but we're really addressing the main concerns through having a potent transgene.

Hung anything to add on that front.

And just one last point here is that I think Jeff you kind of touched on this earlier the captain we're using nationally has pretty broad transtech construction efficiency and so we're not reliant on 81 specific organ or tissue and so we think that having a brock transduction allowance put expression is accretion of this <unk>.

<unk>, so that we can get much more effective cross correction. So again I think.

Jeff Hung: So, again, I think, you know, we'll have a lot more to say in terms of what this particular A-B capsid is in the future, but I think that, for now, I think that, you know, we are very confident that it's going to deliver a very effective gene therapy. Very helpful. Thanks, guys. Great. Thank you, Ritu. Thank you. At this time, I would like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks. Thank you, operator. Thank you, everybody, for listening. Have a great day. Ladies and gentlemen, this concludes today's conference call. Thank you, and have a great day. (inaudible)

We'll have a lot more to say in terms of what this particular achy cap cities in the future, but I think that's where.

For now I think that we are very confident.

Liver it very effective therapy.

Very helpful. Thanks, guys.

Great. Thank you you too.

Thank you.

At this time I would like to turn the conference back to Mister John County, Chairman and CEO for closing remarks.

Great. Thank you operator, thank you everybody for listening have a great day.

Ladies and gentlemen. This concludes for these conference call. Thank you and have a great day.

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