Q4 2018 Earnings Call
Good morning, ladies and gentlemen, and welcome to the Americas fourth quarter and full year 2019 results conference call them because at this time all participants are in they listen only mode.
Operator: Good morning, ladies and gentlemen, and welcome to the Amicus 4th Quarter and Full Year 2019 Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star and then zero on your touchtone telephone.
Later, we'll conduct a question and access session and instructions will follow at that time.
If anyone should require assistance at the conference. Please press Star and then zero on your Touchtone telephone.
Operator: As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Director of Investor Relations. You may begin. Good morning.
As a reminder, this conference call. This being recorded I would now like to turn the conference over to your host Mr., Andrew Fawning Director of Investor Relations you may begin.
Good morning, Thank you for joining our conference call to discuss amicus therapeutics full year 2019 financial results from corporate highlights.
Andrew Faughnan: Thank you for joining our conference call to discuss Amicus Therapeutics' Full Year 2019 Financial Results and Corporate Highlights. Speaking on today's call are John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President and Chief Operating Officer, and Daphne Quimi, Chief Financial Officer. Also joining for Q&A are Dr. Jay Barth, Chief Medical Officer, Dr. Hung Do, Chief Science Officer, and Dr. Jeffrey Castelli, Chief Portfolio Officer and Head of Gene Therapy.
Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer, probably Campbell, President Chief Operating Officer Equally me Chief Financial Officer also joining for Q and I are Dr., Jay Barth, Chief Medical Officer, Dr. Hung do Chief Science Officer, Dr. Jeffs discovery cheap portfolio officer had a gene therapy.
Andrew Faughnan: 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 representations by us that any of our plans will be achieved. Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown 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.
As referenced on slide two you may make forward looking statements then the meeting or the private Securities Litigation Reform Act 1995 relating to our business as well as our plans and prospects are forward looking statements should not be regarded as representations bio that any of our plans will be achieved any or all the forward looking statements made on this call may turn out to be wrong.
It can be affected by inaccurate assumptions, we might make whole 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, we undertake no obligation to revise your I'll keep this presentation in conference call.
Reflect events or circumstances. After the date hereof for full discussion of such forward looking statements and the risk and uncertainties that may impact them. We refer you to the forward looking statements and risk factor section of our annual report on form 10-K for the year ended December 31st 2019 to be filed later today.
Andrew Faughnan: 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, CONFORM 10-K, for the year ended December 31st, 2019, to be filed later today with the Securities and Exchange Commission. At this time, it is my pleasure to turn the call over to Jon Crowley, Chairman and Chief Executive Officer. Jon?
Securities and Exchange Commission.
This time, it's my pleasure to turn the call over to John Ali Chairman and Chief Executive Officer John.
John Crowley: Great. Thanks, Andrew. Good morning, everybody, and welcome to our full year 2019 results conference call. I'll begin on slide three. I'm pleased to highlight the tremendous progress that we've made at Amicus throughout 2019 and now into the start of 2020. In early January, we laid out several key elements and accomplishments for Amicus through 2019 and ultimately bringing us to where we are today in 2020, building one of the next great biotechnology companies poised to impact people around the world who are living with rare diseases. For Amicus, 2019 was another significant period of growth and execution across our science, clinical, regulatory, and commercial efforts, and I'd like to take a moment to highlight just a few of them.
Great. Thanks, Andrew Good morning, everybody and welcome to our full year 2019 results conference call begin here on slide three I'm pleased to highlight the tremendous progress that we've made it and I guess throughout 2019 and now into the started 2020.
In early January we laid out several key elements and accomplishments sporadic is through 2019, and ultimately, bringing us to where we are today in twentytwenty.
Building one of the next great biotechnology companies poised to impact people around the world, we're living with rare diseases.
Frantic is 29 team was eight another significant period or rope execution across our science clinical regulatory and commercial effort.
I'd like to take a moment to highlight just a few of them.
John Crowley: I'll begin with Gallifold. Gallup Hold continues its strong global launch and remains the cornerstone of our success, with $182 million in full-year revenue for 2019. This is the second year in a row that we've exceeded the top end of our revenue guide. For ATGAA, again, that's our next-generation enzyme replacement therapy for Pompe disease and the crown jewel of our portfolio, this continues with significant momentum toward completion of the Phase III PROPEL trial and the potential approval of ATGAA as what we believe will be the new standard of care for people living with Pompe disease. Also, after a strategic review of our business in the second half of last year, we continue to carefully shepherd our financial resources, and we reiterate our cash runway leading us well into 2022 as we continue on a path to profitability.
Begin with Galafold.
Galafold continues its strong global launch and remains the cornerstone of our success.
With $182 million in full year revenue for 2019.
This is the second year in a row that we've exceeded the top end of our revenue guidance.
For 80, G.A. again, that's our next generation enzyme replacement therapy for pump pay disease and the crown jewel of our portfolio. This continues with significant momentum toward completion of the phase three propelled trial and the potential approval into becoming what we believe will be the new standard of care.
Here for people living with pump paid disease.
Also after his strategic review of our business in the second half of last year, we continue to carefully Shepherd, our financial resources, and we reiterate our cash runway, leaving us well into Twentytwenty too as we continue on a path to profitability.
John Crowley: And finally, and very importantly, in 2019, we advanced what we believe to be among the most significant collection of programs, capabilities, and collaborations in the field of gene therapy, including, in 2019, the significant extension of our collaboration with Dr. Jim Wilson and the University of Pennsylvania, as well as important clinical data that we shared in our CLN6 Patent Disease Program. Amicus is the most significant collaborator with the Wilson Lab and Penn
And finally and very importantly in 2019, we advanced what we believed to be among the most significant collection of programs capabilities and collaborations in the feel of gene therapy.
Including in 2019 and significant extension of our collaboration with Dr., Jim Wilson, and the University of Pennsylvania, as well as important clinical data that we shared NRC Olin six batten disease program.
And I guess is the most significant collaborator with the Wilson lab and U. Penn.
John Crowley: We believe that this gene therapy partnership with U Penn and Dr. Wilson provides us with a tremendous research engine for the future growth of amicus. Turning now to slide five, our key strategic priorities for 2020. We have five key strategic priorities this year, and we are well on track to achieving all of them. First, with Gallifold, our precision medicine for fever. We will continue to drive GALIFOLD to more patients living with febrile disease with amenable variants in existing and new markets. We look to achieve global product revenue of $250 million to $260 million this year. 2020
We believe that this gene therapy partnership with U. Penn and Dr. Wilson provides us with a tremendous research engine engine for the future growth dynamic is.
Turning now to slide five our key strategic priorities for Twentytwenty, we have five key strategic priorities this year and we're well on track to achieving all of them.
First we galafold, our precision medicine for Fabry.
We will continue to drive galafold to more patients living with fabry disease with a minimal variance in existing into new markets.
We look to achieve global product revenue this year up 250 million to $260 million.
In 2020, we're off to a strong start thus far and all key metrics are tracking in all key geographies, which give us further confidence in our guidance for this year.
John Crowley: We are off to a strong start thus far, and all key metrics are tracking in all key geographies, which gives us further confidence in our guidance for this year. Second, we are increasing the clinical, regulatory, manufacturing, and pre-commercial activities surrounding our Pompeii program as we advance ATGAA toward approval. In 2020, we are set to complete the Pompeii Phase III Propel study. We are also set to enroll the Pediatric Studies, as well as Advanced Manufacturing, to support a 2021 BLA and MAA filing. Importantly, this year we plan to apply for and initiate a rolling biologics license application or BLA for ATGAA with full clinical results in the first half of 2021 to support a full approval under the fast track designation for this breakthrough therapy designated program. Third, we are advancing our industry-leading rare disease gene therapy portfolio from our new Global Research and Gene Therapy Center of Excellence in Philadelphia.
Second we are increasing the clinical regulatory manufacturing and pre commercial activities surrounding our pump Hey program as we advance 80 G.A. toward approval.
In 2020, we are set to complete the pump paid phase three propelled study.
We are said also to enroll the pediatric studies as well as advanced manufacturing to support a 2021 B.L.A.M.A. violent.
Importantly, this year, we plan to apply for and initiate a rolling biologics license application or B.L.A. for 80, G.A. with full clinical result in the first half of 2021 to support a full approval under the fast track designation for this breakthrough.
I would be designated program.
Third we are advancing our industry, leading rare disease gene therapy portfolio from our new.
Global Research in Gene therapy Center of excellence in Philadelphia, we will be advancing the clinical development manufacturing and regulatory discussions.
John Crowley: We will be advancing the clinical development, manufacturing, and regulatory discussions for both our CLN-6 and CLN-3 BATNs programs. And fourth, in addition, we are progressing our Pompe gene therapy toward IND and will 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, getting us ready to begin clinical studies, we believe, in 2021, as well as with our other potential IND candidates. And we look forward to sharing the additional IND candidates from our UPenn collaboration again later this year.
For both our seal and six and CLM three buttons program.
Fourth in addition, we are progressing our pump hey, gene therapy towards I N D and we'll disclose up to two additional I. Indeed candidates. This year a lot of work is underway with her manufacturing partners for the manufacturing scale up of the pumping gene therapy getting us ready to be.
In clinical studies, we believe in 2021.
As well as our other potential I indeed candidates.
And we look forward to sharing the additional I.M.D. candidates from our U. Penn collaboration again later this year.
John Crowley: And again, we will continue to maintain a strong financial position as we carefully manage our expenses and our investments. Our cash runway is expected to lead us well into 2022 as we continue on a path to profitability, and we are fully funded through all major milestones. On a final note before I hand it over here in a moment to Bradley, Amicus has been very conscious of our global supply chain and even well before the emergence of the coronavirus. There has been no impact on our supply chain for any of our products and no impact on the import or export of our products or essential raw materials. We will continue to monitor the situation closely, of course. Specifically, Gallup old sales remain on track for the year with an adequate supply on hand with respect to the manufacture of ATGAA for Pompeii.
And again, we will continue to maintain a strong financial position as we carefully manage our expenses and our investments.
Our cash runway is expected to lead us well into Twentytwenty too as we continue on a path to profitability.
And we are fully funded through all major milestones.
On a final note before I hand, it over here in a moment to Bradley and it gets has been very conscience, a conscious of our global supply chain and even well before the emergence of the Corona virus.
There has been no impact on our supply chain for any of our products and no impact on import or export of our products or a central raw materials. We will continue to monitor the situation closely of course.
Specifically galafold sales remain on track for the year with adequate supply on hand.
With respect to the manufacturer of 80 GA for pumping.
We and our partners that Wishy biologics has a very robust.
John Crowley: We and our partners at Wooshy Biologics have a very robust, robust risk mitigation plan in place, and there has been no impact on Wuxi's operations in China. Importantly, we have enough supply on hand, stored at our distribution center in Ireland to support the entire Phase 3 PROPEL study and beyond. So, with that introduction, let me now turn the call over to Bradley Campbell, our President and Chief Operating Officer, to highlight Gallup Hold's performance for the year.
Robust risk mitigation plan in place.
And there has been no impact to be she's operations in China.
Importantly, we have enough supply on hand.
Toward at our distribution center in Ireland to support the entire days three propelled study and beyond.
So with that introduction, let me now turn the call over to Bradley Campbell, our President and Chief operating officer, the highlight the Galafold performance for the year.
Bradley L. Campbell: Great. Thanks, John. Good morning, everyone.
Thanks, John Good morning, everyone.
Bradley L. Campbell: Let me begin by providing more color on the continued growth of Gallup Hold for the full year 2019. I'll begin on slide 7 with a global snapshot of the Gallup Hold launch. For 2019, total product revenue was $182.2 million, which is an increase in revenue of $91 million over full year 2018. Gallup's old metrics were driven by exceptionally strong momentum in new countries, including the US and Japan, as well as steady growth in our large early launch countries and our small and mid-sized countries as well. Specifically, the revenue breakdown last year was $129.8 million, or about 71% of revenue generated outside of the United States.
Let me begin by providing more color on the continued growth of Galafold for the full year 2019.
I'll begin on slide seven with a global snapshot of the Galafold launch.
2019, total product revenue was $182.2 million, which is an increase in revenue of $91 million over full year 2018.
Galafold metrics were driven by exceptionally strong momentum in new countries, including the U.S. and Japan as well as steady growth in our large early launch countries and our small and midsize countries as well.
Specifically the revenue breakdown last year was 129.8 million or about 71% of revenue generated outside of the United States and the remaining 52.5 million or about 29% coming from within the U.S. over the full year.
Bradley L. Campbell: and the remaining 52.5 million, or about 29% coming from within the U.S. over the full year. I do want to take an extra minute here to touch on our global commercial reach that we've been building. We now have over 40 countries around the world with regulatory approvals for Galafold, including Argentina, Brazil, Colombia, and Taiwan, which were all approved last year.
I do want to take an extra minute here to touch on our global commercial reach that we've been building. We now have over 40 countries around the world with regulatory approvals for Galafold, including Argentina, Brazil, Colombia in Taiwan, which were all approved last year.
Bradley L. Campbell: We have commercial sales in nearly 30 of those countries, with more on the horizon this year. And we have an incredibly passionate and experienced team working tirelessly to bring our medicines to patients around the world. This expanding global footprint is important not just to support the continued growth of patients with access to Gallifold, but it lays an incredibly strong foundation which is highly leverageable to support the launch of Pompeii and our future products. Turning now to slide eight, I'll recap the performance over 2019. As John mentioned, on the right-hand side of the slide, you can see that 2019 sales nearly doubled, even including a 5% negative impact from foreign exchange. But if you look at that from purely an operational performance perspective, not including FX, we actually more than doubled our sales last year, finishing with well over 1,000 patients on Gallup Hold worldwide. On the left-hand side of this slide, you can see our quarterly performance, which again was very strong in Q4. And again, I think this illustrates the phenomenon we've seen over the past few years that while the quarter-on-quarter growth is relatively nonlinear, it's consistently strong, and we'd expect to see a similar pattern this year.
We have commercial sales and nearly 30 of those countries with more on the horizon. This year.
And we have an incredibly passionate and experienced team working tirelessly to bring our medicines to patients around the world.
This expanding global footprint is important not just to support the continued growth in patients with access to galafold, but it leaves an incredibly strong foundation, which is highly leverageable to support the launch of Pompei and our future products as well.
Turning now to slide eight I'll recap the performance over 2019 as John mentioned on the right hand side of the slide you can see that 2019 sales nearly doubled even including a 5% negative impact from foreign exchange.
If you look at that from purely an operational performance perspective, not including FX, we actually more than doubled our sales last year, finishing with well over 1000 patients on galafold worldwide.
On the left hand side, but this slide you can see our quarterly performance, which again was very strong in Q4 and again I think this illustrates the phenomenon we've seen over the past few years that while the quarter on quarter growth is relatively non linear consistently strong and we'd expect to see a similar pattern. This year.
Now on slide nine was three years of performance behind US we can confidently say, we're on a path to that 500 million sales opportunity in 2023, and as I outlined late last year to get to that 500 million. We expect the five year compound annual growth rate of about 40% from 2018 to 2023.
Bradley L. Campbell: Now on slide nine, with three years of performance behind us, we can confidently say we're on a path to that $500 million sales opportunity in 2023. And as I outlined late last year, to get to that $500 million, 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. That will go a long way towards funding our R&D and OpEx over that period. We also have even further confidence in the $1 billion revenue opportunity at peak for Gallup Hold as we continue to see significant growth in the Fabray market globally. In fact, the global Fabure market for all therapeutics surpassed the $1.5 billion mark in 2019, driven by continued diagnosis from high-risk screening, newborn screening, and other diagnostic initiatives, which we're also investing in as well.
And we expect the generated 1 billion in cumulative revenue between 2000 22022 alone that goes a long way towards funding, our R&D and opex over that period.
We also have even further confidence in the $1 billion revenue opportunity at peak for Galafold as we continue to see significant growth fabry market globally.
In fact, the global Fabry market for all therapeutics surpassed the 1.5 billion dollar Mark in 2019.
Driven by continued diagnosis from high risk screening newborn screening and other diagnostic initiatives, which we're also investing in as well.
Bradley L. Campbell: And, as a reminder, we have orphan exclusivity in the U.S. and Europe, which alone take us to the end of the 2020s, and in addition to our Orange Book listed patents that give us IT coverage into the late 2030s. So a lot of opportunities to provide access to GALFOLD globally for a long period of time. And in the meantime, let me just reiterate that 2020 has gotten off to a great start with all the commercial metrics, including our switch and naive metrics, continued market share growth, and continued high adherence and compliance, all on track to deliver our guidance of $250 to $260 million in global Gallup hold revenues. So with that, let me turn the call back to John to discuss our program updates for ATGA and Pompeii. John.
And as a reminder, we have orphan exclusivity in the U.S. in Europe, which alone take us to the end of the 2020.
In addition to our Orange book listed patents that give us IP coverage into the late 2000, Thirtys. So lot of opportunities to provide access to galafold globally for a long period to calm.
And in the meantime, let me just reiterate the 2020 has gotten off to a great start with all the commercial metrics, including our switching naive metrics continued market share growth and continued high adherence and compliance all on track to deliver our guidance of $250 million to $260 million in global Gulf revenue.
So with that let me turn the call back to John to discuss our program updates for 80 GA in pop that John Great. Thank you Bradley I will begin on slide 11, with 18 gave her pump pay disease again first ever second generation therapy as well as the first therapy for pump a disease ever to received breakthrough therapy designation.
John Crowley: John? Great. Thank you, Bradley. I will begin on slide 11 with ATGAA for Pompe disease, again, the first ever second generation therapy, as well as the first therapy for Pompe disease ever to receive breakthrough therapy designation, or BTD. There is tremendous momentum behind what we believe may be the next standard of care for a broad population of people living with Pompe disease, a product representing a potential one to two billion dollar peak annual revenue opportunity. We are set to complete the POMPEI Phase 3 PROPEL study, enroll the pediatric studies, and advance manufacturing to support the 2021 BLA and MAA filing. It is our plan to apply for and initiate a rolling BLA in the first half of 2021 to support a full approval under the Fast Track designation. Two new updates this morning with respect to ATGAA are, first...
We're BTD.
There is tremendous momentum behind for what we believe maybe the next standard of care for a broad population of people living with pump a disease, a product representing a potential $1 billion to $2 billion peak annual revenue opportunity.
We are set to complete the pump a phase three propelled study.
Enrolled in pediatric studies and advanced manufacturing to support 2021 be allay and EMEA filing.
It is our plan to apply for and initiate are rolling be allay in the first half of 2021 to support a full approval under the fast track designation.
Two new updates this morning with respect to 80 GA. Our first in response to the many requests for compassionate use that we have received for children with infantile onset on pay disease.
John Crowley: In response to the many requests for compassionate use that we have received for children with infantile-onset Pompe disease, it is our plan this year to offer an expanded access program to those in need. Second, our PPQ runs are nearing successful completion with our key strategic partner, WUSHI Biologics, and will serve as the foundation for the Chemistry, Manufacturing, and Control, or CMC, module for a biologic license application for BLA submission. Importantly, we have now successfully completed all three of the bioreactor or upstream production runs under the PPQ process at Wuxi. This is a huge step forward and a major de-risking event for this program. As a reminder, this pivotal PROPEL study, together with additional data that we've collected in the Phase 1-2 studies, will support, we believe, the full approval of ATGAA.
It is our plan this year to offer an expanded access program to those in need.
Second RPP coupons are nearing successful completion with our key strategic partner Wishy Biologics and will serve as a foundation for the chemistry manufacturing and control for CMC module for a biologic license application or be Elyse submission.
Importantly, we have successfully completed now all three of the buyer reactor or upstream production runs under the PQ process. It machine. This is a huge step forward and a major de risking event for this program.
As a reminder, the pivotal propel study together with additional data that we've collected in the phase one two study will support we believe the full approval of 80 GA.
John Crowley: We continue to be extremely excited about ATGAA, as well as our preclinical Pompe gene therapy program to build what we believe could be the largest and most valuable franchise in the industry with the potential to offer a solution to all patients living with Pompe disease globally. So with that, I'd like to turn the call over now to Daphne to review our financial results, guidance, and outlook.
We continue to be extremely excited about 80, GA as well as our preclinical pumping gene therapy program to build what we believe could be the largest and most valuable franchise in the industry with the potential to offer solution to all patients living with pump a disease globally, so with that I'd like to turn.
The call over now to Daphne to review, our financial results guidance and outlook yeah.
Daphne E. Quimi: Thank you, John, and good morning, everyone. Our financial overview begins on slide 14 with our income statement for the full year ending December 31, 2019. For 2019, we achieved Galliford revenue of $182.2 million, which is a 99% increase over the full year of 2018. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 105%, offset by a negative currency impact of approximately 5%.
Thank you John and good morning, everyone. Our financial overview begins on slide 14, with our income statement for the full year ending December 31 2019.
For 2019, we achieved Galafold revenue of 182.2 million, which is 99% increase over the full year 2018.
This includes year over year operational revenue growth measured at constant currency exchange rates of 105% offset by negative currency impact of approximately 5%.
Daphne E. Quimi: Cost of goods sold as a percentage of net sales was 12.1% in 2019 as compared to 15.8% for the prior year. The cost of goods sold as a percent of revenue was favorable as Galliford's revenue continues to grow in the United States, where we do not owe royalties, as well as other countries where we are subject to lower royalties. We continue to make significant investments in R&D and manufacturing with the ongoing pivotal study and commercial scale-up of our POMPEI program, as well as the expansion of our gene therapy portfolio and capabilities. During 2019, we reported $286.4 million in R&D expenses as compared to $270.9 million for the prior year period. The increase is primarily due to continued investments in the Gallup Hold launch, Pompei Clinical Study Program, and our gene therapy pipeline, offset by an up-front payment of $100 million for an asset acquisition that occurred in 2018. Total selling, general, and administrative expense for 2019 was $169.9 million as compared to $127.2 million for the prior year period. The increase represents the expanded geographic scope of the ongoing Galliford commercial launch, including launch activities in Japan and the United States.
Cost of goods sold as a percentage of net sales was 12.1% in 2019 as compared to 15.8% for the prior year.
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 royalties as well as other countries, where we are subject to lower royalties.
We continue to make significant investments in R&D and manufacturing with the ongoing pivotal study and commercial scale up in our Pompei program as well as the expansion of our gene therapy portfolio and capabilities.
During 2019, we reported 286.4 million in R&D expense as compared to 270.9 million for the prior year period.
The increase is primarily due to continued investments in the Galafold launch pump a clinical study program and our gene therapy pipeline offset by an upfront payment of 100 million for an asset acquisition that occurred in 2018.
Total selling general and administrative expense for 2019 was 169.9 million as compared to 127.2 million for the prior year period.
The increase represents the expanded geographic scope of the ongoing galafold commercial launch, including launch activities in Japan, and the United States.
Daphne E. Quimi: On a non-GAAP basis, total operating expenses were $411.8 million in 2019, which was at the lower end of our guidance. This was as a result of careful expense management while also advancing all of our key programs. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation expense, changes in fair value of contingent consideration, and depreciation. The net loss for 2019 was $356.4 million, or $1.48 per share, as compared to a net loss of $349 million, or $1.88 per share, in the prior year period.
On a non-GAAP basis total operating expenses were 411.8 million in 2019, which was at the lower end of our guidance.
This was as a result of careful expense management, while also advancing all of our key program.
We define non-GAAP operating expense as research and development and SDN a expenses excluding share based compensation expense changes in fair value of contingent consideration and depreciation.
Net loss for 2019 was 356.4 million or $1.48 per share as compared to net loss of 349 million or $1.88 per share in the prior year period.
Daphne E. Quimi: As of December 31, 2019, we had approximately 255 million shares outstanding. Turning now to slide 15, as John mentioned, we are fully funded into 2022 through our major milestones in our portfolio and continued global growth. As part of our normal course of business and taking into account all of the new programs that we have integrated into our organization, last year we completed a strategic business review to identify our top priorities and areas of investment to drive efficiencies and cost savings while advancing all of our key programs. We are taking the following actions that extend our cash runway. We will continue to support Galliford revenue growth and have increased confidence around a higher growth trajectory. Through our internal teams and contract manufacturing partners, we have identified synergies and efficiencies in gene therapy development and manufacturing.
As of December 31, 2019, we had approximately 255 million shares outstanding.
Turning now to slide 15, as John mentioned, we are fully funded into 2022 through our major milestones in our portfolio and continued global growth.
As part of our normal course of business and taking into account all of the new program that we have integrated into our organization last year, we completed a strategic business review to identify our top priorities and areas of investment to drive efficiencies and cost savings, while advancing all of our key program.
We are taking the following actions that extend our cash runway.
We will continue to support Galafold revenue growth and have increased confidence around a higher growth trajectory.
Through our internal teams and contract manufacturing partners, we have identified synergies and efficiencies with gene therapy development and manufacturing.
Daphne E. Quimi: We also expect to take a phased approach to build out Amicus facilities, internal manufacturing, and other capital expenditures. We plan to continue our prudent gene therapy portfolio management process to support one to two INDs starting in 2021 and beyond. And as we grow, we are leveraging internal resources and external collaborators for measured internal headcount growth through 2022. Going forward, again to emphasize, we expect total non-GAAP operating expenses in 2020 to remain relatively flat as we leverage the global commercial infrastructure that is already in place for the ATGAA launch and other products in our pipeline, and we transition the costs associated with developing ATGAA to multiple gene therapy programs in our pipeline. And a few comments about our current cash position and 2020 financial guidance.
We also expect to take a phased approach to build out comic its utility.
Internal manufacturing and other capital expenditures.
We plan to continue our prudent gene therapy portfolio management process to support one to two I NDS, starting in 2021 and beyond.
And as we grow we are leveraging internal resources and external collaborators for measured internal head count growth through 2022.
Going forward again to emphasize we expect total non-GAAP operating expenses in Twentytwenty to remain relatively flat as we leverage the global commercial infrastructure that is already in place for the 18.
Hey launch and other products in our pipeline.
And we transitioned the costs associated with development of 88 to multiple gene therapy program in our pipeline.
A few comments about our current cash position in 2020 financial guidance.
Daphne E. Quimi: Cash, cash equivalents, and marketable securities were $452 million at December 31, 2019, as compared to $504 million at December 31, 2018. Looking ahead, we are reaffirming our full-year Gallifold 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 Jon for updates on our next-generation gene therapy platform.
Cash cash equivalents in marketable securities were 452 million at December 31, 2019, as compared to 504 million at December 31st 2018.
Looking at 2020, 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 over to John for updates on our next generation gene therapy platform.
John Crowley: Great. Thank you, Daphne.
Great. Thank you Danielle move now to slide 18, and highlight here our industry, leading portfolio of gene therapies for rare diseases, starting with our batten disease franchise. We have now receive U.S. and you orphan drug designation for both CLM, six and CLM, three batten disease, which together.
John Crowley: I'll move now to slide 18 and highlight here our industry-leading portfolio of gene therapies for rare diseases. Starting with our BATN disease franchise, we have now received U.S. and E.U. orphan drug designations for both CLN-6 and CLN-3 BATN disease, which together with our CLN-1 and CLN-8 programs provide a robust BATN disease franchise that together may represent $1 billion plus in peak recurring annual revenue.
With our CLM, one and seal in eight programs provide a robust batten disease franchise that combined may represent $1 billion plus in Pete recurring annual revenue.
In CLL six we have reported positive interim data in our clinical study that demonstrate meaningful impact of our Avi gene therapy in this devastating form of batten disease.
John Crowley: In CLN6, we have reported positive interim data in our clinical study that demonstrates the meaningful impact of our AAV gene therapy in this devastating form of Batten disease. We have just recently initiated a long-term follow-up of these initial participants, these children in the CLN6 Phase 1-2 study. And this year, we plan to advance regulatory discussions to finalize the clinical and regulatory path forward for this program. The initial CLN6 results provide important readthrough for our clinical study in CLN3-Batin, the most common form of childhood neurodegeneration, where we have safely dosed the initial cohort in addition now to patients in our higher dose cohort.
We have just recently initiated the long term follow up of these initial participants these children in the seal and six phase one two study and this year, we plan to advance regulatory discussions to finalize the clinical and regulatory path forward for this program.
Initial feel and six results provide important read through for clinical study in CLM three baton. The most common form of childhood neuro degeneration, where we have safely dose. The initial cohort. In addition, now to patients in our higher dose cohort.
John Crowley: Our plans this year to advance regulatory discussions and to finalize clinical and regulatory paths for CLN3 and report initial data later this year. On slide 19, I'd like to remind you of the research collaboration with the University of Pennsylvania and the Dr. Jim Wilson Lab, which will be an important driver of growth for Amicus in the future. This collaboration with the Wilson Lab at Penn combines Amicus's protein engineering and glycobiology expertise with Penn's gene transfer technologies to develop novel gene therapies designed for optimal cellular uptake, targeting, dosing, safety, and manufacturability. As part of this collaboration with Penn, Amicus has rights to 50-plus diseases, including 8 currently in active preclinical programs. As highlighted on slide 20, our most advanced program from the Penn collaboration is in Pompe disease. This is moving now into IND-enabling studies, with the potential to enter the clinic in 2021. We expect additional preclinical data out of this collaboration this year in multiple programs, and we are guiding to the disclosure of up to two additional IND candidates by the end of this year.
Our plans this year to advance regulatory discussions and to finalize clinical and regulatory path in CLM three and report initial data later this year.
On slide 19, I'd like to remind you of the research collaboration with the University of Pennsylvania, and the Dr., Jim Wilson lab, which will be an important driver of growth for AMAK is in the future.
This collaboration with the Wilson lab, and combined Amick is protein engineering and glycol biology expertise with tens gene transfer technologies to develop novel Gene therapy is designed for optimal cellular uptake targeting dosing.
Safety and Manufacturability.
As part of this collaboration with U. Penn advocates has rights to 50 plus diseases, including eight currently in active preclinical programs.
As highlighted on slide 20, our most advanced program from the pen collaboration is in pump a disease.
This is moving now into I MD, enabling studies.
With the potential to enter the clinic in 2021.
We expect additional preclinical data out of this collaboration this year in multiple programs and we are guiding to the disclosure of up to two additional R&D candidates by the end of this year.
John Crowley: So, before we turn the call over to Q&A, I'd just like to focus again on people living with rare diseases. We are fighting to bring new hope and alleviate an enormous amount of suffering for many people with rare diseases and for their families. And we are here to deliver on our mission for these patients while creating significant value for our shareholders. So, operating with that, happy to take any questions.
Before we turn the call over to Q and add just like to focus again on people living with rare diseases. We are fighting to bring new hope and alleviate an enormous amount of suffering from many people with rare diseases and for their families and we are here to deliver on our mission for these patients while creating significant value for our shareholders.
So operator with that happy to take any questions.
Ladies and gentlemen, if you have question. Please press star and then the number one key on your Touchtone telephone at this time, we ask that you only ask one question. If you have any additional questions. Please enter back on to the Q.
Operator: Ladies and gentlemen, if you have questions, please press star and then the number one key on your touchtone telephone. At this time, we ask that you only ask one question. If you have any additional questions, please re-enter the queue. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Please hold for your first question. Your first question is from Ritu Baral on behalf of Cowen. Good morning, everyone.
Your question has been answered all you wish to remove yourself from the keel. Please press the pound Keith.
That's all for your first question.
Your first question is from retool, our all with Cowen.
Yeah.
Good morning, everyone. Thanks for taking the question.
Ritu Subhalaksmi Baral: Thanks for taking the question. I wanted to ask about what is left to complete data-wise before you start the rolling BLA. Do you have any outstanding preclinical data for the preclinical module, or is that pretty much set to go? And as far as
I wanted to ask about what is left to complete data wise before you start.
So the rolling be allay.
Do you have any outstanding preclinical data for the preclinical module or is that pretty much set to go and as far as the pediatric study and requirements is that is is that required for approval or is that something that you're aiming for for your desire.
Ritu Subhalaksmi Baral: Is that required for approval or not?
Ritu Subhalaksmi Baral: Is that something that you're aiming for with your desired label? Thanks.
Label.
Thank you got to the left thank you read two to the last part of that question on the pediatric.
John Crowley: Thank you, Ritu. To the last part of that question on pediatrics, that's our own initiative that's not required for approval. That's, we think, important to get this drug into children. We've now been dosing children in the 12, age 12 to 17 cohort. That pediatric study is underway, and we expect now to add additional patients below age 12 all the way down to the expanded access programs that we will initiate here shortly for infantile onset Pompe disease. So not necessary for the full approval, but we think important for the label and important to get it to as many patients as quickly as we can. In terms of what's needed to begin the rolling VLA, there's nothing else of note that would be needed for the preclinical module.
Thats our own initiative that is not required for approval.
Yes, we think important to get this drug into children. We've now been dosing children in the 12 age 12 to 17 cohort that pediatric study is underway. We expect now to add additional patient below that age 12, all the way down to the expanded access programs that we will initiate here shortly for the in Taiwan.
Onset pump a disease, so not necessary for the full approval, but we think important for the label and important to get into as many patients.
As a as quickly as we can in terms of what's needed to begin the rolling via lay there is nothing else of note that would be needed for the preclinical module. So we're in a really good position there and then of course the CMC module is dependent on completing successfully all of those downstream activities for that Bbq.
John Crowley: So we're in a really good position there. And then, of course, the CMC is dependent on completing successfully all of those downstream activities for the TPQ runs. And again, just to remind and reiterate, we have now successfully completed all three bioreactor runs, all the upstream work, which was a major, major undertaking for our team and the WUSHI team, and we are really pleased that that's been done successfully.
And again just to remind did reiterate we have now successfully completed all three buyer reactor runs all the upstream work, which was a major major undertaking for our team in the bouchey team and really pleased that that's been done successfully.
Great. Thanks.
John Crowley: Great, thanks.
Operator: Your next question is from Anupam Rama with J.P. Morgan.
Very well.
The next question is from Anupam Rama with JP Morgan.
Hi on upon this you're talking we can't hear you.
Anupam Rama: Anupam, if you're talking, we can't hear you.
Anupam Rama: Can you hear me?
Can you hear me now.
Anupam Rama: Can you hear me now?
Anupam Rama: Now we can, yeah.
Now we can yes.
Anupam Rama: So, I've gotten this question a few times in the last week or so, but are there any plans to update the Phase I-II Pompeii trial in 2020, or is the next Pompeii update going to be Propel? Thanks so much.
So.
I've gotten this question a lot.
Week, or so but are there any plans to update the phase one two pompei trial, and twentytwenty or the next pump pay update going to be propel. Thanks. So much.
John Crowley: Yeah, I'll let Jay speak to that. We don't have plans right now to update...
Yeah, I'll, let Jay speak to that.
We don't have plans right now to update.
John Crowley: update the Phase 1-2 study at this point.
The phase one two study at this point, we read out to the two year result, which looked very good of course as everyone knows and now we're very focused on completing the phase three trial and getting that out since we can.
John Crowley: Right out.
John Crowley: The two-year results, which look very good,
John Crowley: And now we're very focused on...
John Crowley: trial and getting that out as soon as we can. Yeah, but just to remind everybody, all patients continue, nobody discontinues, everybody continues. Nobody has gone back to Lumizon in that study who were on it before, so anecdotally, we continue to hear positive reports from patients having a good experience on ATGAA. So, again, to Jay's point, we've completed the two-year extension study and are now focused on encapsulating that for the purposes of the BLA and then also collecting significant additional data over the next year for the complete BLA for full approval.
Yeah, but just to remind everybody all patients continue not nobody discontinued everybody continues nobody is gone back to Lumidigm in that study who is on it before so anecdotally we continue to hear positive reports from patients having a good experience on 18, GA, So again to Jay's point Weve.
Completed the two year extension study and now focused on encapsulating that for the purposes of the via leg and then also collecting significant additional data over the next year for the the complete delay for full approval.
Your next question is from Dagan Hall, what the STB Leerink.
John Crowley: Your next question is from Dagan Ha with SBB Larynx. Hey, good morning guys. I hope you can hear me. My one question, and congratulations on all the progress; I just wanted to follow up on the ATGAA aspect. Specifically, as investors are anticipating the Neo-GAA data from Sanofi in the second quarter, John, or maybe even Jay, I wanted to get your take on what are some of the internal scenarios that you have going for the outcomes, and what are some of the respective market opportunities that you currently have modeling for those respective markets.
Hey, Good morning, guys Hope you can hear me.
One question Congrats on all the progress.
Just wanted to follow up on the TJ aspect, specifically as investors are anticipating the neo Jay data from Santa fee in the second quarter.
John or maybe even Jay I wanted to get your take on what are some of the internal scenarios that you have going for the outcomes and what are some of the respective market opportunity that you're currently have modeling for those respective scenarios. Thanks.
John Crowley: Yeah, again, I can't comment on somebody else's program. That data will have to stand or fall on its own right. What I do know is that our program has been in the clinic now since we dosed our first patient in April of 2016. There are now more than 150 people living with pump A on ATGAA.
Yes, again I can't comment on somebody else's program that data will have to standard fall on its own right. What I do know is that our program has been in the clinic now before we dosed our first patient in April of 2016, there now more than 150 people living with pump pay on 80, GA, we expect even.
John Crowley: We expect, you know, even more than that with the pediatric studies this year. Again, one major distinction aside from the difference in the drugs themselves and, frankly, the difference to date in all of the clinical data. The difference, of course, recognized by FDA with the breakthrough therapy designation for our product and Tim's designation in the UK.
More than that with the pediatric studies. This year again, one major distinction aside from the the difference in the drugs themselves.
And frankly, the difference to date and all of the clinical data.
The difference of course recognized by FDA with the breakthrough therapy designation for our product the pins designation in the UK. So I think we'll we're really really competent in 18 gate to be very interesting again, another major distinction, we're studying a range of patients in our propelled phase three.
John Crowley: So I think, you know, we're really, really competent in ATGAA to be very distinct. Again, another major distinction: we're studying a range of patients in our Propel Phase 3, including both switch patients, who make up about 70% of the population for the Propel study, as well as naive patients in that Phase 3 study. So we feel really, really good about where we are. We had no trouble enrolling in our study. We did that with significant wait lists at a number of sites. Again, more than 50 clinical sites on five continents for the Propel study. So we think we have as robust and as successful a program as we can have at this stage.
Including both switch patients, who make up about 70% of the population whether propelled study as well as naive patients in that phase three study. So we feel really really good about where we are we had no trouble enrolling our study we did that with significant weight listed a number of the sites again more.
50 clinical sites on five continents for the propelled study. So we think we have as robust and successful a program as we can have at this stage.
Your next question is from Debjit Chattopadhyay, what the H.C. Wainwright.
John Crowley: Your next question is from Devjid Chattopadhyay with HC Wainwright. Hi, guys. Good morning. This is Aaron from DevJet. Congratulations on all the progress.
Hi, guys. Good morning. This is air enough for Debjit congratulations on all the progress. So we noticed on a world poster that the MX for the six minute walk to us increased with 80 tighter. So that was unexpected do you have any interpretation for this and how does this compare with lumizyme.
Operator: So, we noticed on a world poster that the emacs for the six-minute walk test increased with ADH hider. So, that was unexpected. Do you have any interpretation for this? And how does this compare with Lumizine?
Next question is.
Operator: All right, the next question is about the recent... Hold on, let me stop you. We have one question there. Yeah, we'll answer that one.
But let me stop you about one question there yeah I'll answer that one.
Operator: Jay, I'll let you...
Jay.
Yeah, I mean without getting into the technical aspects of your question, which I don't know if everybody I appreciate but having looked at the antibodies that was something we presented world for in our phase. One two study there was no relationship between the antibodies and efficacy safety or PK.
Jay Barth: I mean, without getting into the technical aspects of your question, which I don't know if everybody can appreciate, but having looked at the antibodies, and that was something we presented at World, for in our...
Jay Barth: In our Phase I-II study, there was no relationship between the antibodies and efficacy, safety, or PK, including
Jay Barth: including the six-minute walk test. Thus, our results stand from our Phase I-II study of showing a very robust effect.
Putting the six minute walk test so our results stand from our phase one two study of showing a very robust effect in efficacy for six minute walk and.
Jay Barth: for a six-minute walk, and that's why, based on Space 1-2 results, we're pretty confident.
That's why based on phase one two results were very confident in the.
Jay Barth: We're very confident.
Jay Barth: in the phase 3 data when that leaves out. Your next question is from Ellie Merle with Cancer Feeds Gerald. Hey guys, thanks so much for taking the question. Just in terms of gene therapy for Fabry disease, can you talk a little bit about the distribution of sort of severity and genotypes and phenotypes in this disease and, you know, in particular, the proportion of patients you think are most suited for gene therapy versus Gallifold and sort of talk about that both as you have your own gene therapy program as well as some competitor programs that are reporting Thanks.
Phase three data when that readout.
Your next question is from Elie Merle with Cantor Fitzgerald.
Hey, guys. Thanks, so much for taking my question just in terms of gene therapy for Fabry disease can you talk a little bit kind of about the distribution.
Very and genotype and phenotype and that he is and in particular and the proportion of patients do you think are most suited for gene therapy.
First of Galafold I'm trying to talk about pop off at the heavier on gene therapy program as loss on kind of competitor programs that are reporting data. Thanks.
Operator: Great. Thanks, Ellie.
Great. Thanks, Kelly I'm going ask Jeff, because deli and Hong to comment in a moment, but in a very high level. We think patients are increasingly very satisfied with galafold and those patients with a minimal variance. We think galafold will for very long time, maybe for their entire lives be the standard of care. We do think there was a real.
Eliana Rachel Merle: I'm going to ask Jeff Castelli and Hung to comment in a moment, but, you know, at a very high level, we think patients are increasingly very satisfied with Gallifold, and those patients with amenable variants, we think Gallifold will be the standard of care for a very long time, maybe for their entire lives. We do think there is a real opportunity, though, to help patients who only have an enzyme replacement therapy, who have the burden of an every-other-week IV infusion, and who have the limitations of the biodistribution of ERTs. For those patients, who represent half or more of the FEBRE population, we do think gene therapy offers potential. It is a significantly complex development path ahead for FEBRE. So maybe, Hung, if you want to describe the technical approach that we're taking in FEBRE, that's another program that we're collaborating with Dr. Wilson and you, Penn, on combining Hung and our science team's expertise in protein engineering with the Wilson lab's expertise in gene therapy. So, Hung, I'll let you comment, and then Jeff, anything to add on the development path and the opportunity in the market? Go ahead.
The opportunity, though to help patients who only have an enzyme replacement therapy, who have the burden of in every other week Ivy infusion, who have the limitations of the bio distribution of the ERP fees for those patients which represent half or more of the February population. We do think gene therapy offers.
Potential it is a significantly complex development path ahead in February so maybe hung if you want to describe the technical approach that we're taking in in February. That's another program that we're collaborating with Dr. Wilson and U. Penn on combining hung in our science teams expertise and protein engineering with.
The Wilson labs that expertise in gene therapy, So hung I'll, let you comment and then Jeff anything to add on the development path and the opportunity in the market.
Sure. Thanks, John and so as you know there's at least half population, who are not appropriate say not amenable to galafold. So we feel we had an obligation commitment to develop and the treatments for those patients and so as John mentioned, we actually are utilizing.
John Crowley: Sure. Thanks, John.
Jeff Hung: And so, as you know, there is at least half of the population who are not appropriate, that is to say, not amenable to Gallifuge. We feel we have an obligation and a commitment to developing a treatment for those patients. And so, you know, as John mentioned, we actually are utilizing our experience and knowledge gained over the past 20 years in regards to understanding lysosomal storage diseases and the actual enzymes, the characteristics that make these particular enzymes effective; we actually are applying those principles to our gene therapy. And so, we intend to make gene therapy with much better targeting and better stability for this particular approach. And then we utilize that in combination with, you know, Drs. Wilson and Tan's expertise in gene delivery.
Experience and knowledge gained over the past 20 years in regards to understanding lysosomal storage diseases and the actual enzymes characteristics that make these particular amazon's effective we actually have flying those principles to our gene therapy. So we intend to make a gene therapy was much better tardy better stability for this particular.
What's particularly approach and then we utilized that income combination was no inductance Wilson pants expertise for gene delivery and so we think the combination of these two could prove to be quite effective to developing novel gene therapy salary Keith.
Jeff Hung: And so, we think the combination of these two could prove to be quite effective to develop a novel gene therapy for thyroid Jeff, anything else to add? No, I think I could just add that we have various studies ongoing right now, preclinically in animal models, looking at different constructs, some with stabilized transgenes, some with targeted transgenes, and we expect lots of that data early this year, and this is one of the programs that we could have a potential IND candidate declared this year based on the outcome of that data, so we're pretty excited, and really, an AAV gene therapy would apply to all patients, but as John mentioned, we think it would really be most probably attractive to patients that are not amenable to Galifold and don't have an oral option, available.
Jeff.
Anything else.
No I think I could just add that we have various studies ongoing right now pre clinically in animal models looking at different constructs somewhat stabilized transgene somewhat targeted transgene and we expect a lots of that data early this year.
And this is one of the programs that we could have the potential Andy candidate declared this year based on the outcome of that data.
So we're pretty excited and really Navy gene therapy would apply to all patients, but as John mentioned, we think it would really be most probably attractive to patients that are not amenable to galafold and don't have an oral option.
Available.
Jeff Hung: I'll just add, too, that we have got a significant amount of experience in the development of medicines for febrile disease, significant reach around the world to all major treatment centers for febrile disease, and, of course, we've got experience now in about 40 countries with getting a medicine for febrile disease approved. So we think that, over, you know, other players in the field, we think that could be another significant advantage for us in addition to the very unique scientific approach that we're taking with Dr. Wilson and UPenn.
Great. Thanks, guys I'll, just add to that we have got a significant amounts of experience in the development of medicines for fabry disease significant reach around the world to all major treatment centers for Fabry disease and enforce we've got experience now in about 40 countries with getting investment for February.
These are for so we think that over other.
Other players in the field, we think that could be another significant advantage for us. In addition to the very unique scientific approach that we're taking with Dr will send anda and Youve pen.
Jeffrey P. Castelli: Your next question is from Mohit Bansal with Citi. Good morning, guys. This is Keevan from Mohit Bansal.
Your next question as from Mohit Bansal with Citi.
Good morning, guys skewed gone from all have thanks for taking your questions I'm. Congrats on the progress this quarter on World I just wanted to ask a quick question. You had mentioned this earlier, but questions on how you're planning to file in 2020 for a TG a limit data might not be available until second half of 2021. Thanks.
Operator: Thanks for taking our questions and congratulations on the progress this quarter and at World. I just wanted to ask a quick question. You may have mentioned this earlier, but questions on how you're planning to file in 2020 for ATGAA when the data might not be available until the second half of 2021. Thanks.
John Crowley: Two things. One, our plan is to initiate a rolling BLA application. We would begin with the first module, the preclinical module, followed by the CMC module, and then in the first half of 2021, when we will have the propelled data. We would then use that data in the first half of 2021 to complete the BLA submission with the clinical section. Again, that's for full approval for a very wide patient population, both pediatric and adult, and we would expect, with a fast track designation, that that would be about a half-year review time from there.
Two things one this our plan is to initiate a rolling BLA application, we would begin with the first module. The preclinical module followed by the CMC module and then in the first half of 2021, where we will have that propelled data we would then.
Is that data in the first half of 2021 to complete the be allay submission with the clinical section again, that's for full approval for a very wide patient population, both pediatric and adult and we would expect also with the fast track designation that that would be about a half a year review time from.
Operator: Your next question is from Whitney Ijim with Guggenheim. Hey guys, thanks for taking the question. So on CLN6, I apologize if I missed it, but should we expect a data update there in terms of...
There.
Your next question is from Whitney Ijem with Guggenheim.
Hey, guys. Thanks for taking my question so on CLM.
Hi, Paul will buy multiple but should we expect the data update there in terms of additional follow up and also on the natural history data and then kind of what are the rate limiting steps there before you sort of start you engage regulators.
Operator: [inaudible]
Operator: And then kind of what are the rate-limiting steps there before you sort of start to engage regulators in thinking about next steps?
John Crowley: Sure. Thanks, Whitney.
How about next steps.
Sure. Thanks, Whitney So we expect in the second half of this year to have long term follow up data on the 13 patients who have been treated with GE or with the gene therapy NCL and six.
John Crowley: So we expect in the second half of this year to have long-term follow-up data on the 13 patients who've been treated with the gene therapy in CLN6. Lots of other activities that would be necessary for VLA filing, including a lot of activities around manufacturing. And again, we expect, probably in the second half of the year, to be able to articulate what's required for a VLA submission.
Lots of other activities that would be necessary for a BLE filing, including a lot of activities around the manufacturing to remind everybody. Our partner there is thermo Fisher scientific in their Brammer Division.
We're now well underway nearly complete with all the tech transfer in the scale up activities with the GMP manufacture in hyper stacks of that gene therapy. So a lot of activity is on the manufacturing and the CMC side would be necessary for a delay and again, we expect probably in the second half of the year.
Operator: Your next question is from Yan Zong with the Janney. Hi, thanks for taking the question. So, the PROPEL study is enrolling both speech patients and naive patients, so I wonder, are you able to disclose whether more speech patients or more naive patients have been enrolled and in the phase 1-2 study, have you ever looked at whether it's a cohort combined, including both switch patients and NARIC patients instead of individual cohort
To be able to articulate what is required for would be a light submission.
Your next question if somebody on song with Janney.
Hi, Thanks for taking a question so.
How study is enrolling both which patients and naive patients so I wonder.
Are you able to disclose.
Wars switch patients or more now you patient have become wrote and in the phase One study have you ever looked at.
In cohort combined.
John Crowley: Sure, thanks, Jen. To remind everybody, the PROPEL Phase 3 study for ATGAA over-enrolled, and it enrolled a total of 123 patients. About 70% of them were switch patients from ERT standard of care, and about 30% were treatment-naive.
Putting both switch patient and occupation instead of individual cohorts.
Sure. Thanks, again to remind everybody that propel phase three study for 80, GA over enroll and enrolled a total of 123 patients about 70% of them are switch patients from ERP standard of care about 30% or treatment naive.
John Crowley: Yes, to your second question, the Phase I-II study had separate cohorts for naive patients and switch patients. They weren't in one cohort, but they were in the same study, and therefore, we were able to take that data, and that was the basis for the Phase III study design that included switch patients and naive patients. And the results that we saw were very favorable for both switch and naive in the Phase I-II study. We are, as I said, very confident going along in the PROPEL study towards seeing results for both switch and naive. It will be, in a primary analysis, combining both those populations in the Phase III study in PROPEL.
Jay.
Yes.
Yes to your second question the Phase one two study had separate cohorts for naive patients and switch patients.
They weren't in one forward, but there were in the same study and therefore, we able to take that data and that was the basis for the phase three study design that included the switch patients and the nave patients and the results that we saw were very favorable for both which I know you've in the phase one two study. So we are that vary.
Company going.
Along in the propel study towards seeing the results in both switch and naive.
It will be in the primary analysis, combining both those populations in the phase three study and propel gets pretty straightforward actually again, if you just look at the we had the 10 patients in cohort one in the phase one to those are the switch patients ambulatory switch and our cohort three were five ERP treatment naive patients are we.
John Crowley: Yeah, it's pretty straightforward actually, and if you just look at the 10 patients in cohort 1 in phase 1-2, those are the switch patients, ambulatory switch, and our cohort 3 were 5 ERT treatment nave patients. We saw, I think, Jay, if I remember correctly, a 6-minute walk, I think it was 9 out of 10, 8 or 9 out of 10, at one year, who showed improvements on APGAA, again, very different from what you'd expect to be a decline based on multiple natural history studies that have been done. And our phase 3 were 5 out of 5 showed improvements at one year, on 6, significant improvements at one year. So, if you were to combine that, adding the nave would only make it look stronger.
So I think Jay if I remember its six minute walk I think it was nine out of 10, eight or nine out of men at one year, who showed improvements on a TJ again very different from what you'd expect to be a decline based on multiple natural history studies that have been done and our phase three were five at a five showed improvement that one.
Sure.
On fixed significant improvements at one year, so if you're to combine that adding the naive would make it only looks stronger.
Operator: Your next question is from Salveen Richter with Goldman Sachs. Hi, thanks for taking the questions. This is Andrea on behalf of Salveen. Could you speak a little bit about the GALFOLD naive switch dynamics, where you stand with respect to increasing that proportion of naive patients and if there have been any gating factors there? And then, I'm wondering if you could comment on the launch dynamics for GALFOLD in the Latin American geographies and if you're still expecting meaningful revenue contribution there in 2021 plus. Thank you.
Your next question is from Salveen Richter with Goldman Sachs.
Hi, Thanks for taking the questions. This is Andrew on for Salveen could you speak a little bit about the galafold naive such dynamics, where you stand with respect to increasing that proportion.
Naive patients and if there if any gating factors there and then I'm wondering if you could comment on the launch dynamics for Galafold into Latin American geographies, and if you're still expecting meaningful revenue contribution there and 20 or 21 class. Thank you.
Yes, great question. So first on the dynamics between switch and naive patients. The last update we gave which was for full year was 66% of patients were switch and 34% Werent naive patients and that's that's on track really with our strategy as you may recall.
Bradley L. Campbell: Yeah, great question. So first on the dynamics between switch and naive patients, the last update we gave which was for full year was 66% of patients were switched and 34% were naive patients and that's that's on track really with our strategy as you may recall which is when we launch we target switch patients first. They're already in the system getting their infusion every other week and so that's the lion's share of patients within the health care system and then as we move along we start to to target the naive patients or previously untreated patients. So if you look at our more mature markets like Europe as an example, the EU five countries, there we're starting to see an equal contribution of switch and naive patients coming on to Galliford, whereas in countries like you know
Which is when we launch we target switch patients first are already in the system getting their infusion every other week and so that's the lion share patients within the healthcare system and then as we move along we started to target the naive patients or previously untreated patients. So if you look at our more mature markets like Europe as an example, the U five country.
There were starting to see an equal contribution of switch and naive patients coming on galafold, whereas in countries like the United States in Japan, I, we're still seeing a predominant.
Bradley L. Campbell: in Japan, we're still seeing a predominant uptake in switch patients first, although we are seeing strong uptake in naive patients as well. So that's a dynamic that we continue to expect to play out in three or four years from now. We would expect to start to see perhaps more naive patients coming on Galliford as we've maximally penetrated into the switch market. So that's the sort of switch na
Uptake and switch patients first although we are seeing strong uptake in naive patients as well so that that's a dynamic that we continue to expect to play out in three or four years from now we would expect to start to see perhaps more naive patients coming on galafold as Weve Max Max we penetrated into the switch.
Okay. So that's the sort of switch dynamic and again as well within our strategy and continues to move wealth.
Bradley L. Campbell: And again, it's well within our strategy and continues to move well. From a Latin American perspective, as we mentioned, we did get some key approvals last year in Argentina and Brazil, and we would expect to begin to, and we've already seen some named patient sales in those markets, we would expect to start to see commercial sales in those markets. We will caveat, though, as a reminder, in Brazil, as we seek national reimbursement, we're still in that judicial review process, which takes about a year for patients to go all the way through. And so that's why we've said we expected 2021 to begin to be a significant growth driver in the Latin American market. So, nice foothold so far, continuing to open up access for patients in those markets, but again, we'd see 21, 22 as when those would really start to meaningfully contribute to overall revenue.
From a Latin American perspective, as we mentioned we did get some key approvals last year in Argentina and Brazil.
And we would expect to begin to and we've already seen some named patient sales in those markets. We would expect to start to see commercial sales in those markets. We will copy out though as as a reminder, in Brazil as we seek national reimbursement, we're still in that judicial review process, which which takes about a year for patients to go all the way through.
And so Thats why Weve said, we've expected 2021 to begin to be a significant growth driver from from the Latin American markets. So nice foothold so far continuing to open up access for patients in those markets, but again, we see 21 22 as window that really start to meaningfully contributed to the.
Overall revenue.
Your next question is a follow up from Debjit Chattopadhyay with H.C. Wainwright.
Operator: Your next question is a follow-up from Deb Chatterpahe with H.C. Wainwright. Hey guys, just real quick, not sure if I missed this in your prepared remarks, but was there, of the 182 million in fiscal year 19 revenue, how much of that is U.S. versus ex-U.S.? and Anfor2020.
Hi, guys just real quick not sure if I missed this in your prepared remarks, but was there a 182 million fiscal year 19 revenue how much of that is U.S. versus ex U.S.
And for 2020.
Operator: Sure, we've reported. We did cover that. We'll repeat it. No problem. Daphne, please.
Sure. We've reported we Didnt cover that will repeat is no problem definitely yes sure. So so the U.S. portion of that is approximately 30% an ex us would be the remainder 70%.
Daphne E. Quimi: Yeah, sure, so the U.S. portion of that is approximately 30%, and the ex-U.S. would be the remainder 70% of revenue.
Revenue, we haven't given specific guidance as to the breakdown us versus ex us that kind of 70 30 number is.
Daphne E. Quimi: We haven't given specific guidance as to the breakdown of U.S. versus ex-U.S. That kind of 70-30 number will probably hold relatively stable. We're continuing to grow outside the United States in terms of the base of countries that contribute. Of course, the U.S. continues to launch well, so that's kind of right in the zone. It might move around a little bit from there, but I would expect that to be pretty
We'll probably hold relatively stable.
Team to grow outside the United States in terms of base of countries that contributed to of course, you asked continues to launch well, so thats kind of right in the zone it might run a little bit from there, but but I expect that to be pretty consistent this year.
At this time I, what I would now like to turn the conference back over to Mr., John Crowley, Chairman and CEO for closing remarks.
Operator: At this time, I would like to turn the conference back over to Mr. John Crowley, Chairman and CEO, for closing remarks.
John Crowley: Great. Thank you, Operator. Thank you, everybody, for listening. As you can see, it was a great 2019, and we're off to a really strong start on all metrics in 2020. Thanks for listening. Have a good day.
Great. Thank you operator, thank you everybody for listening as you see it was a great 2019, and we're off to a really strong start on all metrics in 2020. Thanks for listening have a good day.
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