Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics Second Quarter 2020 Financial 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.

[Operator Instructions] 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..

Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics’ second 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; and Dr.

Jeff Castelli, Chief Development Officer. 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.

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 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 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 June 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?.

Thank you, Andrew. Good morning and welcome everyone to our second quarter 2020 results conference call. As we did last quarter let me start by stating that I hope everybody and their families are well and safe.

Our leadership team at Amicus continues to emphasize a range of programs and initiatives to protect and support our global workforce during this ongoing pandemic.

While adapting to all of the changes brought about by the global pandemic, for Amicus the first half of 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 efforts as we continue to build one of the next great global biotechnology companies 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 Galafold continues its strong launch performance and remains the cornerstone of our success with $62.4 million in second quarter revenue. The Galafold launch continues to exceed expectations.

Second quarter revenue represents the performance across the global business including new patient starts from both switch and treatment naive patients throughout the quarter in all major regions including those hardest hit by COVID-29. Second, our R&D timelines remain on track.

We continue to expect Phase 3 PROPEL study of AT-GAA in late onset Pompe disease to read out in the first half of 2021. Additionally the rolling BLA submission for AT-GAA remains on schedule and we expect the first submission later this year.

Within our gene therapy pipeline we continue to move forward our lead Batten disease programs for CLN6 and CLN3 as well as our most advanced pre-clinical programs in gene therapy. And third, following our strategic financing in July, Amicus cash position is sufficient now to achieve profitability without the need for any future diluted financings.

Our continued revenue growth, prudent expense management and growth potential has allowed us to reach this important milestone of self-sustainability as we continue to realize our vision of delivering groundbreaking and potentially curative new medicines for people living with rare diseases around the world.

Turning now to slide 4, we are well on track to achieve our five key strategic priorities for 2020 including first Galafold, our precision medicine for Fabry disease. We will continue to drive Galafold to more people living with Fabry disease with the minimal variance in existing and new markets around the world.

We look to achieve global product revenue this year of $250 million to $260 million. Second, we are increasing the clinical regulatory manufacturing and pre-commercial activities and planning surrounding our Pompe program for AT-GAA as we move this important therapy towards approval.

Third, again we are advancing our industry-leading rare disease gene therapy portfolio sending from our new global research and gene therapy center of excellence in Philadelphia we will be advancing the clinical development, manufacturing and regulatory discussions for both our CLN6 and CLN3 Batten programs.

Fourth, in addition we are progressing our Pompe gene therapy towards IND and we plan to disclose up to two additional IND candidates this year. A lot of work is underway with our manufacturing partners for the manufacture and scale up of the Pompe gene therapy as well as our other potential IND candidates.

So again we look forward to sharing the additional IND candidates from our PENN collaboration later this year. Fifth, again we will continue to maintain a strong financial position as we carefully manage our expenses and our investments and we remain fully funded now to profitability.

So with that before I turn the call over to our team to provide more detail on the strong quarter I just wanted to take a moment to acknowledge Dr. Ted Love's retirement from the Amicus board of directors. Ted as many of you know is a remarkable leader, a great friend of mine and a fierce advocate for innovation for patients.

Ted and I will continue to work closely together as the Chair and Vice Chair of the emerging company section on the Bio board and I would very personally like to thank him for his nearly decade of service on our board. He has helped to put Amicus in a much stronger position. So thank you Ted.

With that let me turn the call now over to Bradley Campbell our president and chief operating officer to further highlight the strong Galafold performance.

Bradley?.

Great. Thanks John. Good morning everyone. As John mentioned I will now walk you through in more detail our Galafold performance for the quarter and let me start on the continued growth of Galafold revenue in the second quarter of 2020 here on slide 6 and this is where we give our global snapshot of the Galafold commercial progress.

For the second quarter as John mentioned total product revenue was $62.4 million driven by strong patient demand, favorable reimbursement dynamics and business continuity even during the worst quarter of COVID so far and importantly our global compliance and adherence rates continue to exceed 90%.

The geographic breakdown of revenue during the quarter was $41.5 million or 67% of revenue generated outside the United States and the remaining $20.8 million or 33% coming from within the United States. On a sequential basis you'll note that ex-U.S. quarterly revenue did decline slightly from Q1 to Q2 due to the timing of orders.

However, we continue to see strong growth in patients added during second quarter and that strength has continued now into the first month of Q3. So we expect to finish the year around 70/30 ex-U.S. to U.S. sales.

As a reminder we have now over 40 countries around the world with regulatory approvals and commercial sales now in over 30 of those countries and this expanding global footprint is important not just to support the continued growth of patients with access to Galafold but it really lays a strong foundation that is highly leverageable to support the potential launch of AT-GAA, for Pompe and our future products as well.

One other interesting aspect of the expanding market access to Galafold which is highlighted on this slide and this is quite unique is that we now have added over 1,000 additional amenable mutations to the European label. The previous 300 mutations were all associated with specific patients who'd been identified with those mutations.

These new mutations represent nearly all of the possible mis-sense mutations in the GLA gene that are amenable to Galafold as determined by our amenability assay.

So the physician now diagnoses a new patient with one of these mutations, they'll no longer have to wait for us to characterize the mutation and run it through the amenability assay; a process which previously could take several months.

Now the physician can simply refer to the website and check the amenability of the mutation and the patient can get immediate access to Galafold. Again a really exciting application and a really unique application of the pharmacogenetic aspects of this medicine and one that we're looking to apply to other geographies as well. Turning now to slide 7.

We've had a very strong quarter even in the face of the COVID-19 epidemic pandemic. Our global supply chain remains fully intact.

Our customers have great confidence that they can access Galafold and our field team has been able to achieve a significant portion of their pre-COVID touch points through digital, telephonic and other means of interacting with their physicians.

All of this has led to continued uptake with new patient starts all throughout the crisis in both switch and treatment naive youth patients. Even in the hardest hit countries like the UK, France, Italy, Spain, Japan, U.S.

and many others we are able to bring on patients to Galafold throughout the quarter and it's important to note that on a country by country basis as local conditions allow and in a very carefully prescribed manner, we're now allowing our field organization to go back out to visit their physicians in key accounts.

We believe that these dynamics may continue to provide some tailwinds even as the evolving global pandemic inevitably has caused some headwinds which will continue to closely monitor as the full impact of the pandemic currently remains unknown.

From a numbers perspective, you can see that the second quarter sales increased 41% from second quarter 2019 which does include a 2% negative impact from foreign exchange. So from a true operational perspective sales increased by 43% compared to last year.

On the left-hand side we show our quarterly performance over the past several quarters and as we've mentioned on previous calls while we continue to expect strong growth quarter-to-quarter due to a variety of factors the rate of growth is typically non-linear.

Looking to the back half of the year as we've seen in many years past we expect a higher quarter-on-quarter growth in Q4 as compared to Q3 which means we expect the larger portion of the revenue in the second half of the year will fall into the fourth quarter.

But overall as we've just finished the seventh month of the year here in July we continue to be very confident in our guidance of $250 million to $260 million in full year global sales.

Now on slide 8, with several years of performance behind us and now launched in most major markets around the world we can confidently say we are on a path to that $500 million sales opportunity in 2023.

As I've outlined previously to get to that $500 million we expect a five-year average CAGR of about 40% from 2018 to 2023 and we expect to generate $1 billion in cumulative revenue between 2020 and 2022 alone which goes a long way towards funding our R&D and OpEx over that period.

We also have even further confidence now in the $1 billion revenue opportunity at peak as we continue to see significant growth in the Fabry market globally driven by continued diagnosis from high-risk screening, newborn screening and other diagnostic initiatives in addition to penetration into the diagnosed untreated population.

As we have orphan exclusivity in the U.S. and Europe in addition to our multiple orange book listed patents that give us IT coverage into the late 2030s so we have lots of opportunity to provide access to Galafold for a long period to come. With that let me hand the call now over to Dr.

Jeff Castelli our chief development officer who will further highlight our lead pipeline programs.

Jeff?.

Yes. Thanks Bradley and good morning everyone. Moving on to our R&D updates on slide 10, we wanted to remind everyone of our highly differentiated Pompe therapy AT-GAA and its mechanism of action.

At-GAA is our novel next generation therapy consisting of ATB200 or cipaglucosidase alfa an investigational human recombinant GAA enzyme designed to target muscle cells throughout the body administered via IV infusion combined with AT2221, an orally administered enzyme stabilizer.

AT2221 is administered shortly before the infusion of ATB200 begins and is intended to bind and stabilize ATB200 in circulation allowing more active enzymes to be taken up into cells and delivered to lysosomes.

The combination of ERT and enzyme stabilizer is one major distinction from the standard of care and other treatments in development for Pompe. The other and we believe potentially more impactful distinction is the unique carbohydrate profile of the enzyme itself. Dr.

Hung Do, our chief science officer and his team have been working over the past decade to develop a Pompe ERT which improved binding the target receptors for efficient uptake in the cells while importantly retaining the ability of the ERT to be processed by those cells after it's taken up to the mature more active form of GAA.

With that in mind and now turning to slide 11, we would like to highlight a recent publication in the molecular therapy methods and clinical development journal where [Dr.

Nina Ravens] team at the National Institute of Health published findings from an independent pre-clinical study building upon previous work with AT-GAA that showed additional improvements with longer term treatment to knockout mice.

The study showed that AT-GAA was successful in completely reversing excess glycogen accumulation restoring muscle strength and significantly improving a cascade of secondary abnormalities including the elimination or reduction of autophagic built-up in muscle fibers, improvements and markers of lysosomal damage and in self-signaling.

These are particularly exciting findings as these impacts had not been observed in previously disclosed studies. Finally, on slide 12 we want to remind everyone of the integrity of our Pompe Phase 3 PROPEL clinical trial. We reiterate that study timelines remain on track with data expected in the first half of 2021.

To-date more than 97% of the 2,800 plus planned infusions and all study assessments for the ongoing PROPEL study have been completed on schedule.

Additionally, we continue to enroll patients in our pediatric studies and advanced manufacturing to support a 2021 BLA and MAA we want to express thanks to all our Pompe clinical study participants and their families to all our investigators and their staff and to our cross-functional Amicus Pompe team for their collective unwavering commitment and supportive efforts in this unprecedented time.

Moving on now to slides 14 and 15, I will 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 Pompe and Fabry gene therapy programs with University of Pennsylvania.

Starting with our Batten disease franchise and CLN6, we previously reported positive interim data in our clinical study that demonstrates meaningful impact of our AAV gene therapy in this extremely devastating form of Batten disease.

In October at the virtual child neurology society annual meeting we're expecting additional data from the CLN6 Phase 1, 2 Study. We continue to advance regulatory discussions to finalize the clinical and regulatory path and expect to provide an update in early 2021.

We believe this initial CLN6 data provides important read through for a clinical study in CLN3 Batten disease which is the most common form of childhood neurodegeneration. We plan to report initial data from the ongoing Phase 1 to CLN3 study early next year based on scheduling changes for some of the major gene therapy conferences.

Concurrent with the data early next year we will provide the expected regulatory paths for the CLN3 program. We continue to make great progress on all of our commercial manufacturing process for both CLN6 and CLN3 and remain on track to begin dosing additional patients in both of these programs next year.

Moving on to slide 16, I would like to remind everyone of the research collaboration with the University of Pennsylvania which will be an important driver of growth for Amicus 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 of novel gene therapies that are designed for optimal cellular uptake, targeting, dosing, safety and manufacture ability.

As part of this collaboration anecdotes has rights to over 50 different diseases in addition to the active ongoing pre-clinical programs. Several Amicus presentations were given at the American Society of Gene Cell Therapy annual meeting back in the second quarter.

This data was highlighted by our Pompe gene therapy results which showed the Amicus engineered GAA protein had improved targeting and clearance of glycogen storage in Pompe disease in mice.

Additionally, preliminary data and non-human primates suggested therapeutically relevant expression levels in target organs which is a key factor as you move to larger species. We remained very encouraged by this data and continued to progress our Pompe gene therapy towards an IND.

We also continue to make progress across our pre-clinical gene therapy program and look to disclose up to two additional IND candidates later this year. With that I would like now to turn the call over to Daphne to review our financial results, guidance and outlook.

Daphne?.

Thank you Jeff and good morning everyone. Our financial overview begins on slide 18 with our income statement for the quarter ended June 30, 2020. For the second quarter we achieved Galafold revenue of $62.4 million which is a 41% increase over the second quarter of 2019.

This includes year-over-year operational revenue growth measured at constant currency exchange rates of 43% offset by a negative currency impact of 2%. Cost of goods sold as a percentage of net sales was 10.8% in the second quarter as compared to 12.1% 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 owe royalties as well as in other countries where we are subject to lower royalties.

Total operating expenses were $107 million in the second quarter of 2020 which decreased as compared to $115.2 million in the second quarter of 2019. On a non-GAAP basis total operating expenses were $95.9 million in the second quarter of 2020 as compared to $103.6 million in the second quarter of 2019.

The decrease in research and development cost reflects decreased travel and third-party costs offset by continued investments to support the PROPEL study and in our gene therapy pipeline.

Our investment in research and development includes the impacts of the implementation of the cost reduction measures that were previously announced as does the decrease in selling, general and administrative expenses.

Due to the timing of expenses the non-GAAP operating expense is expected to increase in the third quarter of 2020 as compared to the second quarter of 2020. We define non-GAAP operating expense as research and development and SG&A expenses excluding share-based compensation, changes in fair value of contingent consideration and depreciation.

Net loss for the second quarter was $52.5 million or $0.20 per share as compared to net loss of $84.6 million or $0.36 per share for the prior year period. As of June 30, 2020 we had approximately $257 million shares outstanding.

Turning now to slide 19 as John mentioned following our $400 million senior secured term loan facility we are now on a clear path to profitability without the need for any future salute of financing.

As we initially laid out last year at our analyst day we have achieved this milestone by our continued revenue growth with Galafold as well as driving efficiencies, cost savings and careful expense management.

Securing the 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 first leverage the commercial infrastructure that is already in place for the AT-GAA launch and other products in our pipeline.

Secondly, we transition the costs associated with the development of AT-GAA to multiple gene therapy programs in our pipeline and third maintain financial discipline while meeting our objectives.

To reiterate all high priority research programs in gene therapy are moving ahead on schedule especially in CLN3, CLN6, Pompe and Fabry and we continue to fully support the work with Jim Wilson and PENN. A few comments about our cash position and 2020 financial guidance.

Cash, cash equivalents and marketable securities were $309.6 million at June 30, 2020 compared to $452.7 million at December 31, 2019. Following the receipt of net proceeds from the July debt facility and retiring the prior term loan of $150 million Amicus has a cash position of over $530 million as of July 31.

We are reaffirming our full year Galafold 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 let me turn the call back to John for closing remarks..

Great. Thank you, Daphne, Jeff and Bradley. So as you can see we have been relentlessly focused on performance across the business despite all of the unprecedented change and challenges that have been brought about by the global pandemic.

We have a great global team of passionate entrepreneurs at Amicus who have led and will continue to lead us through this. 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 any questions. .

[Operator Instructions] Your first question comes from the line of Anupam Rama from JPMorgan. Your line is now open..

Hey guys. Thanks so much for taking the question. Just a quick question on the PROPEL study. For those small number of patients who did not get an on-time infusion, scheduled infusion, did these patients ultimately get an infusion outside of the window? Or was it just a skip infusion and then they got the next one? Thanks so much..

Sure. Jeff maybe I will ask you to [field] that question. Again Anupam to state that even in preparing for the study as with most clinical studies and the statistical analysis plan we expected more than 3% of the infusions would be missed that's just kind of common in any study certainly in rare disease studies.

So even with COVID-19 we're performing better than we expected from an infusion and an assessment standpoint but maybe Jeff could speak to the very-very few missed infusions..

Sure. Thanks John and thanks Anupam.

That 3% number could refer to either entirely missed infusions or it could be an infusion that was slightly out of the every two week window but importantly as part of the initial study design we had allowed for individual study subjects to have some small number of missed infusions and to still remain in the primary analyses and in the study and everything we've seen fits within what we had.

It was even better than what we had planned pre-COVID for potentially having patients initially infusion. .

Yes. That’s remarkable on Pompe even through the height of the early days of the crisis in March and April, we had so very few missed infusions that I think that was a real testament to patient motivation, desire to participate in the study, desire to access these medicine, investigator efforts and just some remarkable efforts by our team.

Again if you remember back then we really came up with a patient-by-patient, site-by-site plan to maintain the integrity of that study. So we're really pleased where we are today..

Your next question comes from the line of Ritu Baral from Cowen. Your line is now open..

Good morning, guys. Thanks for taking the question. I will take the flip side to Anupam's question and ask about the assessment specifically six minute walk at the final time point necessary for the primary endpoint.

Can you talk about how many of those specifically have been completed? How many of them might have been out of spec and the timing of, the number and timing of those that are planned for Q3? Since we don't know how COVID is going to go, I'd love to know how many of them are so to speak in danger..

Yes. We probably can't provide that level of granularity or two in terms of who's due for which assessments on which date or in which quarter but I'll just then I'll ask Jeff to comment here. Virtually all of the six minute walk test assessments were done and completed on time within the window particularly those again those 12-month assessments.

We were in the March and April timeframe where that was a real concern we went to extraordinary lengths to make sure that those assessments occurred. So very-very few, I think maybe it was one or two patients may have fallen out of that window. So it should have no impact on the study and again as expected in a study like this.

Jeff any color you'd like please?.

Yes. John you covered it very well.

I'll just remind everyone that as we plan the study and the statistics as you do with any clinical trial you assume some amount of missing data due to dropouts, missed visits and we are well within what we had planned even before we over enrolled the trial from 100 to 123 and as John said that 97% plus implies not only to infusions but also just scheduled study assessments and particularly six minute walk is the primary endpoint and that month 12 everyone is really pitching together, make sure those are going off on track.

So we're in a great place in terms of available date and patients for the final PROPEL analysis..

Yes. Importantly Ritu we've had virtually no dropouts in the study and again you typically in that statistical plan will plan for up to 10% of study participants or more to drop out. So that will certainly help us a great deal as well and also gives us a great margin for those very few patients who may have missed assessments..

And 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 question.

So as you think through the gene therapy program for Pompe, any thoughts on the relative contributions of the bis-M6P glycosylation versus pH stabilization with migalastat and would you consider keeping patients as and when the gene therapy program goes in the clinic on a sort of a stable background dose of migalastat based on the PROPEL experience? Thank you..

Yes Debjit, so we looked very carefully and did some pretty exhaustive studies pre-clinically to look at the relative contributions of the new enzyme that we had developed with the enhanced glycosylation and the improved targeting with the high levels of nano-six phosphate together with the Chaperone and again remember the mechanism here is that the improved glycosylation and the high levels of nano-six phosphate are what's necessary for the enzyme to move from the blood to move from the plasmid to target those receptors on muscle and to be internalized and absorbed into all key muscle tissues so that would be skeletal, that would be diaphragmatic, that would be in patients with cardiac, involvement cardiac absorption as well.

And we think that the great majority of the benefit 80%-90% I think is what Hung is characterized of the benefit is due to the enhanced nature of the absorption of the enzyme. It's the glycobiology. We do think the Chaperone plays an important function and in all of our pre-clinical studies we saw enhanced breakdown of glycogen.

So we think the function of the Chaperone is to enhance the stability of the protein in plasma potentially to make it better tolerated but also when it does deliver it to the lysosome it delivers it in a more active form which again contributes to even greater glycogen breakdown.

So again that's part of the novelty of the combination therapy here but again we think the great benefit for patients, the preponderance of the benefit is in the glycosylation of the enzyme..

Hey this is Jeff. I'll just add basically to that as you apply that towards gene therapy which I think the question also might have been asking about similarly to AT-GAA we think majority of the benefit there is the engineer transgene was the well-targeted GAA.

A difference with gene therapy versus the enzyme replacement therapy is that rather than only giving a dose of enzyme every two weeks with gene therapy the enzyme is sort of constantly secreted out from the transduced cells into the blood. So it's not quite as simple to think how a Chaperone might help with the gene therapy.

So right now our vision for the Pompe gene therapy is just as a gene therapy not combined with a stabilizer but there is some theoretical potential where you could look to use a stabilizer but right now that's not our plan..

Yes. You also could in some diseases that we're looking at where the enzymes are even more inherently unstable in plasma, you could potentially engineer stability into those transgenes and that's one aspect of the technology that we're exploring for some other disorders..

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

Great. Thanks for taking my question and congrats on all the progress despite pandemic. Maybe one question of on Sanofi side because now that we have data from the neo GAA program, one thing -- at least in my mind is getting clear is that how inadequate the existing treatments are for Pompe disease, especially Lumizyme which was the control here.

So with that in mind do you have any updated thoughts about the control arm for PROPEL study and the powering assumptions here because if I'm not mistaken you are assuming control to be relatively stable here.

Is that fair for treatment experienced patients at this point?.

Thank you, Mohit. I'm not going to comment on any of the neo data. I think that data will speak for itself.

You did reference to the Lumizyme control arm that was a surprising finding in that study that at the 12 month endpoint the control arm the Lumizyme again in treatment naive patients showed if I recall just that maybe it was a two meter improvement which is less than has been seen in any previous studies, the approval study, the late onset study or LOT study showed.

I think it was 20 or 25 meter improvement that's what we built into our powering assumptions for the cohort of patients, the treatment naive patients in our study. We assumed Lumizyme would perform much better than it did in that common study. So and that's what's built into our stats.

If it does worse of course that will only enhance our ability to show the distinction with AT-GAA and Jeff add any color or comment?.

No, John you covered that perfectly..

And your next question comes from the line of Ellie Merle from Cantor Fitzgerald. Your line is now open..

Hey guys thanks so much for taking the question and congrats on all the progress.

Just one on Fabry disease, just in terms of I know you mentioned for Galafold you're seeing sort of improvements in the diagnosis rate and treatment rate, I'm curious, I guess the current diagnosis and treatment rate that you're seeing broadly in your addressable markets as well as just based on the recent trends you're seeing what sort of a realistic assumption to think about for a long-term penetration in this market given sort of pretty under-diagnosed and under-treated currently right now, so how we think about kind of peak entrance and in light of potential gene therapy competitors how you see this disease landscape evolving? Thanks..

Yes. Again it remains I think a great opportunity to help a lot of people living with Fabry disease as more and more experience is being had with Galafold and importantly more and more patients are being identified. We continue to believe that Fabry is one of the most if not the most under or misdiagnosed human genetic diseases in existence.

So Bradley, I'll let you comment specifically about the growth potential here and what we're planning for..

Yes. Ellie thanks for the question. I think there's sort of two pieces of your question. First is penetration of treatment into the diagnosed population and then the second is percentage of potential Fabry patients who are diagnosed. I'll take the first one first, I think it's a little bit easier.

There I think we'll see high penetration of treatment into the diagnosed population.

I think as we've been able to introduce a small molecule into the space we've been able to grow the treated market even since we've been on the market and I think at the end of last year we shared that of the thousand plus patients on Galafold 300 of them were diagnosed but previously untreated.

And I think you see that analogy, play out in other markets as well if you look at the MS space with the introduction of TECFIDERA the other small molecules even if you look further back and at PAH with the introduction of the [indiscernible] class of molecules, you see significant growth of treated patients of the diagnosed population.

Separate and we think we'll see that in Galafold as well. Separate from that if you ask the question of what percentage of potential Fabry patients will be diagnosed, we know that number is growing.

We've seen ourselves other manufacturers in the space spend a lot of time both looking at newborn screening but also looking at high risk population screening and we've talked a lot about that before in kidney populations, in cardiac populations in MS and pain clinics. So we see that a lot of efforts are going into that.

That being said, if you look at newborn screening and you see that this is a potentially one in 1,500 one in 3,000 live birth incidents. I would suspect that unfortunately it will continue to be an under diagnosed disease for years to come that could imply a global incidence of a 100,000 Fabry patients.

So I think we would do a great job to continue to chip away at that diagnosis rate but I think that would be a journey that all of us go on over the next decade or so..

And your next question comes from the line of Mike Ulz from Baird, your line is now open. .

Hey guys thanks for taking the question. .

Good morning Mike..

Good morning. Just a quick question on AT-GAA and you're rolling BLA, you're still on track to start that in the second half of this year. Wondering if you can give us a sense of what you plan to file this year? I'm just curious if you think that you'll be in a position to kind of have the majority of the BLA filed prior to the Phase 3. Thanks..

Yes. As we know there are really three key sections to the biologic license application or BLA. The first is the pre-clinical module. Second is the CMC module and third will be the full clinical. We expect that the full pre-clinical including all the toxicology work has been completed.

That will form the foundation for the first part of the filing this year. We expect then the second filing for the CMC section and again we've completed all of the PPQ runs successfully. So a significant part of the work and frankly a significant part of the risk has been taken out of that.

So we feel really good about where manufacturing is and our partners at Wuxi Biologics with our tech-ops and quality teams have really just done a remarkable job at the commercial scale up here.

So we expect that then to go in the first half of next year and then the last section to go in also in the first half of next year would be the full clinical. So hopefully that answers your question Mike.

So we'll be in really good shape with that rolling BLA beginning this year and completed in the first half the full BLA in 2021 followed very quickly thereafter we hope with by the MAA filing in Europe..

[Operator Instructions] Your next question called from the line of Anvita Gupta from Guggenheim Securities. Your line is now open..

Hi guys, congrats on the quarter and hope you all are doing well. My question is on the Batten programs.

What is the extent of the additional data from the CLN6 that we will be able to see at the CNSA in October and if you could maybe talk about how many patients worth of data and how long of a follow-up does the FDA want to see in your discussions for the regulatory path forward in both CLN6 and CLN3? Thank you..

Yes. I will ask Jeff to comment in a moment on the data that we'll see if child neurology this fall in Anvita and again we are engaged in discussions both for CLN6 and CLN3 with the U.S. FDA. We expect to complete those this year and now very early next year to be able to share that. I'm not going to comment on the ongoing discussions.

We've always said that we know we want to, we need to treat additional patients with our commercial scale material. That material will be available in the first half of 2021.

So we expect it will be a relatively small number of patients and I don't yet have an answer for what the duration of that treatment period would be that would be sufficient then with a BLA filing.

But we continue to have great confidence in this program is being on a really good path for people living with both CLN6 and CLN3 with those two respective gene therapies.

Jeff, do you want to comment on the data for CLN6, the updated data that we will see?.

Sure. Thanks John. So just as a reminder last year at the CNS Annual Meeting we presented data on the first eight patients that had been treated and that was with anywhere from one to two years of follow-up. So this year we'll have one to two years of follow-up data in all 13 treated patients and the majority of that will be year two of follow-up.

In addition, we'll have more natural history data in comparisons to also put the data from these 13 kids into context as to what would have been expected based on the natural history..

And your next question comes from the line of Dae Gon Ha from BTIG. Your line is now open..

Great. Thanks very much for taking the questions. Sorry I missed this John but in the press release when you talk about now 1,000 plus mutations included in the EU label for Galafold, can you maybe help us understand what percentage of the Fabry patients that encompasses, I think the previous number was 35% to 50%.

And concurrently any updates to the FDA label as it pertains to the number of mutations.

And then the second question is as we look toward your Pompe gene therapy that that everyone's looking forward to, I was wondering if you can provide a little bit of context or maybe some insights as to your internal discussions with regards to say goals such as less than [10 e14 vector genomes per KIG] or trying to avoid [AAV8] as a vector outright, thanks..

Sure. All right. I think you squeezed three questions in there. So let me break those apart. On the first part for the mutations the addition here, I would not expect that this increases the market size or the relative percentage of patients with amenable mutations. It will just help us accelerate treatment to those patients once they are identified.

So we still believe up to about half of people living with Pompe disease are living with an amenable mutation. So again this completes the work necessary to expand that label.

Bradley do you want to comment on where Jeff's on the FDA when we would expect any label update there with those additional mutations?.

Yes John. The FDA is a slightly different process. So we are essentially as we had been doing in Europe, we're essentially adding batches of additional mutations that we identify. So this year we'll send in a quite large batch of new mutations that have been identified with patients into the FDA but it's a different regulatory process.

So we'll continue to share that as we have those updates. We are looking to do a similar kind of global update as we did in Europe with some other geographies outside the United States and that'll take place over the course of this year and into next as well.

But as John said I think the most important thing is these updates really provide facilitated access for patients. So rather than having to go through the individual characterization of the new mutation and then getting it into the label or onto the website this kind of batch process really allows that to be much faster for patients and physicians..

And then relative to your question around the Pompe gene therapy that continues to progress very well. We've said all along that gene therapy and Pompe disease is much needed but it's also incredibly complicated given the nature of this disease.

We built our gene therapy work in Pompe disease around our collaboration with Jim Wilson and if you remember going back about two years, it was one of the original three programs that formed the foundation of our initial collaboration with Dr. Wilson.

One key element of that collaboration was our belief that we needed to not only deliver properly targeted and ultimately effective gene therapies, we needed to make sure we could do it safely. Particularly in a disease like Pompe, given the compromised nature of the patients and the need likely for systemic delivery of an AAV.

So we've always been focused on enhancing the targeting through the novel transgenes that we have enhancing the targeting of the enzyme that's produced by the gene therapy vector so that we can have a low or as lower dose as possible.

So with that maybe Jeff you want to comment around what we and Jim believe around this? Obviously there is been a lot of difficult news in this space from others in the gene therapy field that I think only highlight the importance of proper targeting and safety. So Jeff I'll turn it to you. .

Sure. Thanks John. John noted from the beginning our approach in gene therapy has been to design more potent gene therapies based on either stabilization or better targeting for uptake to keep systemic doses in a range that are as low as possible.

We've said previously that as we went into things based on the guidance from our colleagues at PENN we had an upper ceiling in the range of 5e13 per kilogram based on all the existing data. Pre-clinically that's been reported as well as clinically. We still think that that's a likely ceiling.

I think there will be more and more learning as people process through the recent data from the authentic study the very high dose systemic gene therapy to figure out how you really scale across weights and ages of kids but we remain committed to trying to make more potent gene therapy so we can keep hopefully systemic dosing in that one to five e13 per kig range that we think has some established safety..

Your next question comes from the line of Ritu Baral from Cowen. Your line is now open..

Hey guys, thanks for taking the follow-up. I wanted to ask maybe I'm reading too much into it but in the CMC portion of your presentation John, I think -- did you imply that there are still outstanding CMC activities to be completed before the BLA filing? And also where are you on additional manufacturing sources outside China? Thanks..

Yes. I will let, we're in a really good place on both of these but I'll let Bradley comment.

Brad do you want to, do you get those?.

Yes sure. On the first one, we had previously said that, all the upstream and manufacturing portion of the PPQ sections were complete and that drug product was released that was all according to spec and to our analytical compatibility agreements. We do have the drug product.

PPQ runs at the lyophilization process that's a much more straightforward process. It's a much faster process that's underway and should be complete here shortly. That's kind of the last manufacturing step. Of course you have to pull together the package and submission and that's all on track and per the protocols that we agreed to with the agencies.

And I think John answered a question previously on the rough timing for when we hope to complete that section.

In terms of the manufacturing capabilities outside of China, as we discussed previously WuXi has invested in a similar manufacturing facility in Dundalk, Ireland and the manufacturer of that facility is well underway and the intention is for that facility to be licensed right around the time of our anticipated approval, so that you would, the first launch material would come out of the WuXi facility in WuXi, China and then as we get into the first couple of years of commercialization that would be complemented by the Irish, the material coming out of the Ireland plant.

So you'd very quickly have two sources of manufactured goods.

I would remind you though we've also already begun the process of moving product outside of China into our various regional hubs and then down even to the site level where appropriate that was done in part to make sure we had product in various regions but also has been very important from a continuity of supply perspective for the challenging times of COVID and that's how we've really been able to maintain that uninterrupted supply chain even through the worst of the COVID impact..

Thank you Bradley, hopefully that's clear that everything remains on the timeline that we've laid out previously and so far everything remains on track both for the activities to support the CMC section of the BLA as well as the scale up and now we're continuing to build commercial inventory so that hopefully at launch we'll be able to provide the medicine to all patients in need and part of that is the capacity planning to make sure that we have dual sources of manufacture and again as Brad noted that remains on track with the Ireland plant moving forward as well.

I was supposed to be in Ireland next week actually to visit that plant..

And your next question comes from the line of Anvita Gupta from Guggenheim Securities. Your line is now open..

Hi guys thanks for the follow-up.

Just following up on Ritu’s question but on manufacturing on the gene therapy side and apologies if I missed this earlier if I have, could you comment on your efforts in building the in-house gene therapy manufacturing capabilities and if we might see a hybrid manufacturing model first and then probably a completely in-house? Thank you..

Thanks Anvita and that's exactly what we're evolving to as we began in the working two years ago in the gene therapy space, we relied for our initial materials in Battens on materials supplied by nationwide children's.

We've then gone through an exhaustive review of the entire supply chain including plasmid producers and ultimately the contract manufacturers. We as you know, work very closely with our partners at Brammer Thermal Fisher. I have been enormously impressed with their capabilities and their growing capacity.

They will supply the material for us on a commercial basis for the CLN6, CLN3 Batten's programs. We're also working with them now on other programs including for instance our Pompe gene therapy manufacturing. While we're doing that in parallel as we are evaluating sites for our own in-house manufacturing.

We're actually designing now a Phase 1, 2 manufacturing facility. We will have more to say about that in the months ahead, as well as looking forward beginning the basis of design for a larger commercial scale facility.

I continue to believe that if you're going to be one of the world's leading companies in the field of genetic medicine and gene therapies, you also need to be one of the world's experts in the manufacturing of those gene therapies and again this was something Amicus has been uniquely suited for with our more than 75 people at Amicus working in technical operations, manufacturing and quality having gone through for the last seven years, the design scale up and manufacture now at commercial scale and quality for AT-GAA one of the most complicated glycosylated proteins ever manufactured, we've done that successfully.

So we really think we can translate many of those skills and capabilities at Amicus now to become one of the world's leading manufacturers for gene therapy. So it's been a very carefully thought through strategy and one that we remain on track for. Thank you..

And there are no further question at this time. I would like to turn the conference back to Mr. John Crowley Chairman and CEO for his closing remarks..

Great. Everybody thank you for the great questions. I hope everybody and your family remain healthy and again we had a really strong second quarter and look to finish out a really strong second half of the year. Thanks everybody. Have a great day..

Ladies and gentlemen this concludes today's conference call. Thank you and have a great day..