Q1 2021 Amicus Therapeutics Inc Earnings Call
Operator: Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics first quarter 2021 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. If anyone should require assistance during the conference, please press a star and then zero on your touchscreen telephone. As a reminder, this conference call is being recorded moment. I would now like to turn the conference over to your host, Mr. Andrew Fawney, head of investor relations. You may begin.
Good morning, ladies and gentlemen, and welcome to the amicus Therapeutics first quarter two CASM for any one 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, Inc.
And why should require assistance during the conference.
Star and then zero on your Touchtone telephone as a reminder, this conference call is being recorded I would now like to turn the conference over to your host Mr. Andrew Funny head of Investor Relations you may begin.
Andrew Faughnan: Thank you, Mary. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' first quarter, 2021 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 Cuey, Chief Financial Officer, and Dr. Jeff Costelli, Chief Development Officer, joining for Qumelie.
Thank you Mary Good morning, Thank you for joining our conference call to discuss amicus Therapeutics first quarter 2021 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 Queenie, Chief Financial Officer and Dr.
For Jeff Castelli, Chief Development Officer, joining for Q&A, we'll have Dr. Mitchell Goldman Senior Vice President of clinical research joining as referenced on slide two we may make forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects are forward looking statements should not be regard.
Andrew Faughnan: We'll have Dr. Mitchell Goldman, Senior Vice President of Clinical Research, joining us. As referenced on slide two, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. However, our forward-looking statements should not be regarded as representations by us that any of our plans will be achieved.
That's representation by us that any of our plans will be achieved and you're all the forward looking statements made on this call may turn out to be wrong and can be affected by interest 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.
Andrew Faughnan: None of our plans will be achieved. And here, 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.
Andrew Faughnan: You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the full forward-looking statements and risk factors section of our annual report on Form 10K for the year ended December 31st, 2020, and the quarterly report on Form 10Q for the quarter ended March 31st, 2021, 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.
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 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, 2020, and our quarterly report on form 10-Q for the quarter ended March 31, 2021 to be filed later today for 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.
John Crowley: Great, thank you, Andrew. Good morning, and welcome everyone to our first quarter 2021 results conference call. I'm pleased to report that the first quarter of 2021 reflects execution across the key strategic priorities that we outlined at the beginning of the year. As we did in this morning's press release, I'd like to highlight several key accomplishments. First, Gellifold continues its strong launch performance and remains the cornerstone of our success. With $66.4 million in first quarter revenue, we're very pleased with the continued momentum of Gallifold uptake globally.
Great. Thank you Andrew Good morning, and welcome everyone to our first quarter 2021 results conference call I'm pleased to report that the first quarter of 2021 reflects execution across the key strategic priorities that we outlined at the beginning of the year.
As we did in this morning's press release I'd like to highlight several key accomplishments.
First gala fold continues its strong launch performance and remains the cornerstone of our success with $66 $4 million in first quarter revenue were very pleased with the continued momentum of the Gallup poll uptake globally.
John Crowley: The number of patients on Gallifold at the end of the quarter continued to exceed our internal expectations, despite continued headwinds from COVID-19, as well as uneven ordering patterns. Additionally, our key regulatory timelines for ATGA remain on track, and our R&D pipeline of gene therapies continues to advance. Following a successful pre-BLA meeting and written communication with the USFDA, we continue with our plans to complete the rolling BLA submission of ATGAA in the second quarter of this year and anticipate additional regulatory submissions in the European Union and in other geographies throughout 2021. We continue to have great confidence in ATGAA to benefit people living with Pompeii disease, and we intend to move it rapidly through regulatory submission. Onward towards approval.
The number of patients on Gallup poll at the end of the quarter continued to exceed our internal expectations. Despite continued headwinds from COVID-19, as well as uneven ordering patterns.
Second our key regulatory timelines for a T. G. A a remain on track and our R&D pipeline of gene therapies continues to advance.
Following a successful pre BLA meeting and written communications with the U S. F. D. A we continue with our plans to complete the rolling BLA submission of a T. G. A a in the second quarter of this year and anticipate additional regulatory submissions in the European Union.
In other geographies throughout 2021.
We continue to have great confidence in eight T. G. A a day benefit people living with Pompe disease, and we intend to move it rapidly through regulatory submissions onward towards approval.
John Crowley: Within our gene therapy pipeline, we continue to further our lead batten disease programs for CLN6 and CLN3, as well as our most advanced pre-clinical gene therapy programs. Through our broad research collaboration with Dr. Jim Wilson and the University of Pennsylvania, we are highly encouraged by the preclinical data and progress from our February and Pompeii disease gene therapy clinical candidates. We are pleased to share that new preclinical data from both programs will be presented at ASGCT this week. Third, the amicus cash position is sufficient to achieve self-sustainability without the need for any future dilutive financing.
Within our gene therapy pipeline, we continue to further our lead batten disease programs for C. L. N six N C. L N three as well as our most advanced preclinical gene therapy programs.
Through our broad research collaboration with Dr. Jim Wilson, and the University of Pennsylvania, We are highly encouraged by the preclinical data and progress from our Fabry and Pompe disease gene therapy clinical candidates.
We are pleased to share that new preclinical data from both programs will be presented at a S. G. C. T. This week.
Third the amicus cash position is sufficient to achieve self sustainability without the need for any future dilutive financings.
John Crowley: Our continued revenue growth, prudent expense management, and growth potential have allowed us to reach this important milestone as we continue to realize our vision of delivering groundbreaking and potentially curative new medicines for people living with rare diseases around the world. And, finally, as we announced just a few days ago, I'm very pleased to welcome our new Senior Vice President of Strategy and Business Development, Sebastian Martel, to the Amicus team. Sebastian served most recently as global head of rare diseases at Sanofi Genzyme and brings deep expertise in corporate strategy, business development, and commercialization. We look forward to Sebastian's contributions to advancing Amicus' mission for patients as a leading global biotechnology company. Turning to slide four.
Our continued revenue growth prudent expense management and growth potential has allowed us to reach this important milestone.
As we continue to realize our vision of delivering groundbreaking and potentially curative new medicines for people living with rare diseases around the world.
Finally, as we announced just a few days ago and I'm very pleased to welcome our new senior Vice President of strategy and business development Sebastien Martel to the amicus team.
Sebastian served most recently as global head of rare diseases at Santa Fe, Genzyme and brings deep expertise in corporate strategy business development and commercialization, we look forward to sebastian's contributions to advancing amicus as mission for patients is a leading global biotechnology company.
Turning to slide four.
John Crowley: We are well on track to achieve our five key strategic priorities for 2021. These include Gallifold, our precision medicine for February; we will continue to drive Gallifold to more people living with February disease with amenable variants in existing and new markets. We look to achieve global product revenue of $300 million to $315 million this year, which reflects the strong momentum and demand behind this precision medicine globally, despite some COVID-related disruptions that we saw in the latter part of 2020, which continued into early this year.
We are well on track to achieve our five key strategic priorities for 2021.
These include.
Gallup polled our precision medicine for Fabry.
We will continue to drive Gallup poll to more people living with fabry disease with amenable variance in existing and new markets. We look to achieve this year global product revenue of 300 million for $315 million, which reflects the strong momentum and demand behind this precision medicine globally.
Despite some COVID-19 related disruptions that we saw in the latter part of 2020, and which continued into early this year.
John Crowley: Second, we remain steadfast and passionate in our commitment to advancing ATGA through global regulatory submissions for the benefit of as many people living with Pompeii disease as quickly as possible. Third, we are advancing our industry-leading rare disease gene therapy portfolio. Again, stemming from our global research and gene therapy Center of Excellence in Philadelphia, we will be advancing the clinical development, manufacturing, and regulatory discussions across multiple programs in our gene therapy pipeline.
Okay.
We remain steadfast and passionate in our commitment to advancing a T. G. A a true global regulatory submissions for the benefit of as many people living with Pompe disease and as quickly as possible.
Three we are advancing our industry, leading rare disease gene therapy portfolio.
Again stemming from our global research and gene therapy Center of excellence in Philadelphia, we will be advancing the clinical development manufacturing and regulatory discussions across multiple programs in our gene therapy pipeline.
John Crowley: Four, in addition, we are progressing our manufacturing capabilities and capacity to build world-class technical equipment to support all gene therapy programs. And five, finally, again, we continue to maintain a strong financial position as we carefully manage our expenses and investments, and we remain fully funded through all major milestones. So with that introduction this morning, let me now hand the call over to Bradley Campbell, our president and chief operating officer, to further highlight the Gallifold performance. Bradley. Great, thanks, John, and good morning, everyone.
For in addition, we are progressing our manufacturing capabilities and capacity to build world class technical operations to support old gene therapy programs.
And five finally again, we continue to maintain a strong financial position as we carefully manage our expenses and investments and we remain fully funded through all major milestones.
So with that introduction. This morning, let me now hand, the call over to Bradley Campbell, our President and Chief operating officer to further highlight the Gallup polled performance Bradley.
Alright, Thanks, John and good morning, everyone as John.
Bradley L. Campbell: As John mentioned, I'll now walk you through our Gallifold performance for the quarter. On slide six, we have a global snapshot of the Gallifold commercial. For the quarter, total product revenue was $66.4 million, driven by strong patient demand and business continuity, despite quarter over quarter revenue being impacted by the typical uneven ordering patterns from Q4 to Q1 that were slightly exacerbated by COVID. And I'll provide a little bit more detail on that.
John mentioned I'll now walk you through in more detail our <unk> performance for the quarter on slide six we have a global snapshot of the Gallup hold commercial progress for the quarter total product revenue was $66 $4 million driven by strong patient demand and business continuity despite quarter over quarter revenue being impacted by the typical uneven ordering.
Patterns from Q4 to Q1 that were slightly exacerbated by COVID-19 and I'll provide a little bit more detail on that in a moment.
Bradley L. Campbell: The geographic breakdown of revenue during the quarter was $45.5 million, or 69% of revenue generated outside of the United States, and the remaining 20.9 million, or 31% coming from within the United States. As we've mentioned before, we expect that split to continue to be roughly 70-30, and we continue to grow both parts. Turning now to slide seven, Q1 was another quarter of global growth, and the number of patients on Gallifold at the end of the quarter was ahead of our internal escalation.
The geographic breakdown of revenue during the quarter was $45 $5 million for 69% of revenue generated outside of the United States and the remaining $29 million or 31% coming from within the United States. As we've mentioned before we expect that split to continue to be roughly 70 30.
We continue to grow both parts of the business.
Turning now to slide seven Q1 was another quarter of global growth and the number of patients on Gallup hold at the end of the quarter was ahead of our internal estimates.
Bradley L. Campbell: The business continues to be incredibly resilient with patients added in all of our territories. As I alluded to, first quarter revenue reflected increased patient demand, although it was slightly offset by timing of orders in some ex-US geography, reauthorizations in the United States, and some irregular ordering patterns due to COVID. Specifically, we did see some larger orders in Q4 as relates to Brexit and COVID. Both of these have now largely worked their way through the system in Q1. But that did accentuate the typical year-end work.
The business continues to be incredibly resilient with patients added in all of our major markets.
As I alluded to first quarter revenue reflected increased patient demand that was slightly offset by timing of orders and some ex U S geographies reauthorization in the United States and some irregular ordering patterns due to COVID-19.
Specifically, we did see some larger orders in Q4 as it relates to Brexit and COVID-19 respectively.
Both of these have now largely worked through the system in Q1.
But that did accentuate the typical year end ordering phenomenon.
Bradley L. Campbell: We also had a couple of large orders in the last days of Q1 that sounds like, These examples are consistent with our expectation of nonlinear, quarter to As we highlighted in our full year call, with the resurgence of COVID in the fourth quarter and into Q1, we did see some slowdown and new patient starts due to delays at the point of care between patient identification and initiation of treatment. Importantly, though, our supply chain remains fully intact. Our customers have confidence that they can access Gallifold, and our field team has been able to achieve a substantial majority of their pre-COVID touchpoint through a combination of in-person, digital, telephonic, and other means of interacting with physicians. We, of course, continue to monitor the pandemic's impact, but the good news is that today we've observed improvements in the latter part of the first quarter and into the beginning In the United States, the month of April saw the largest number of prescription requests since before the pandemic.
We also had a couple of large orders in the last day as of Q1 that sounds for Q2.
These examples are consistent with our expectation of non linear quarter to quarter growth.
As we highlighted in our full year call with the resurgence of COVID-19 in our fourth quarter and into Q1, we did see some slowdown in new patient starts due to delays at the point of care between patient identification and initiation of treatment.
Importantly, though our supply chain remains fully intact, our customers have confidence that they can access gallon sold and our field team has been able to achieve a substantial majority of their pre COVID-19 touch points through a combination of in person digital telephonic and other means of interacting with physicians.
We of course continue to monitor the pandemic impacts, but the good news is today, we've observed improvements in the latter part of the first quarter and into the beginning of the second quarter specifically.
Specifically and I think this is really important because it reflects what we've been saying about strong underlying demand.
In the United States. The month of April saw the largest number of prescription requests since before the pandemic.
Bradley L. Campbell: And in our ex-US business, we've seen a steady increase in rolling average monthly new patient starts from the last 12 months to the last six months and now to the last. Based on this momentum and continuing to anticipate a second half recovery from COVID, we're confident in meeting our full year 2021 guidelines. Although, again, we do expect that quarter to quarter growth will be nonlinear throughout the year, on slide nine, we've called out several of the drivers and metrics which lay the foundation for our continued growth in 2021.
And in our ex U S business, we've seen a steady increase in our rolling average monthly new patient starts from the last 12 months to the last six months and now for the last three months.
Based on this momentum and continuing to anticipate a second half recovery from COVID-19. We are confident in meeting our full year 2021 guidance. Although again, we do expect debt quarter to quarter growth will be non linear throughout the year.
On slide nine we've called out several of the drivers and metrics, which lay the foundation for our continued growth in 2021.
Bradley L. Campbell: It really starts with the momentum from 2020, where we finished with over 1,400 patients on Gallowhold and opened up several new launches. Now, with over 1,400 patients on Gallifold, we're at about a 49% global market share of treated amenable patients. So while we're achieving higher market shares in countries where we've been approved the longest, there's still plenty of opportunity to continue to switch patients over to GELP. We also know that there are significant numbers of diagnosed, untreated patients who have amenable mutations, and we now have a global mix of about 60% switch and 40% of Gallifold patients who were previously naive.
It really starts with the momentum from 2020, where we finished with over 1400 patients on Gallup polled and opened up several new launch countries.
Now with over 1800 patients on Gallup polled were at about a 49% global market share of treated amenable patients.
So while we're achieving higher market shares in countries, where we have been approved the longest theres still plenty of opportunity to continue to switch patients over to gallon sold.
We also know that there are significant numbers of diagnosed untreated patients who have amenable mutations.
And we now have a global mix of about 60% switch and 40% of <unk> patients who were previously naive to treatment.
Bradley L. Campbell: As we've said before, over the next few years, we expect that rate of switch in naive patients to move to about 50-50. And in the long term, we expect to see that percentage reverse in favor of naive patients as we continue to fuel market growth. All of that is underpinned by compliance and adherence rates that continue to exceed 90%, reiterating that our belief, those patients who go on gallows hold stay on gallows.
As we've said before over the next few years, we'd expect to see that rate of switch and naive patients to move to about 50 50 and in the long term, we expect to see that percentage reverse in favor of naive patients as we continue to fuel market for us.
All of that is underpinned by compliance and adherence rate adherence rates that continue to exceed 90% reiterating that our beliefs that those patients who go on galaxy fold stand golf fold.
We think the value of <unk> has been well recognized by payers with nearly 100% of insurance reauthorization is being granted now in 2021 with U S payers and a similarly strong track record of successfully negotiating and renegotiating reimbursement.
Bradley L. Campbell: We think the value of Gallup Hold has been well recognized by payers, with nearly 100% of insurance reauthorizations being granted now in 2021 with U.S. payers, and a similarly strong track record of successfully negotiating and renegotiating reimbursement agreements outside the United States. Our relentless focus on ensuring access to Gallup Holds continues to be a major, Another important driver of growth for Gallifold is continued geographic expansion. In 2021, we expect to add at least five additional countries as we look to expand access to Fabry patients with amenable variants around the world, and we expect to see continued traction in our newer launch markets in Latin America, Asia-Pacific, and of course, the U.S., Japan, and the rest. As a reminder, Gallifold has received regulatory approval in over 40 countries and commercial sales in over 30 of those today.
<unk> outside the United States.
Our relentless focus on ensuring access to gallon sold continues to be a major strength.
Another important driver of growth for Gallup hold US continued geographic expansion in 2021, we expect to add at least five additional countries as we look to expand access to fabry patients with amenable variance around the globe.
And we expect to see continued traction in our newer launch markets in Latin America Asia Pacific and of course U S, Japan and the rest of the world.
As a reminder, gal holders received regulatory approval in over 40 countries and commercial sales in over 30 of those today.
So really despite the recent COVID-19 related headwinds in certain geographies demand for <unk> worldwide has never been stronger now with some cues of potential new Gulf old patients building in some geographies and we're confident in our guidance of $300 million to $315 million and full year global sales.
Bradley L. Campbell: So really, despite the recent COVID-related headwinds in certain geographies, demand for Gallifold worldwide has never been stronger, now with some cues of potential new Gallifold patients building in some geographies, and we're confident in our guidance of 300 to 315 million in full-year global sales. As part of that guidance, we project net new patient starts this year will be even greater than 2020. And we expect this growth in patients and corresponding revenue to be delayed to the second half of the year as COVID's impact continues.
As part of that guidance, we project net new patient starts this year will be even greater than 2020 and.
And we expect this growth in patients and corresponding revenue to be weighted to the second half of the year as COVID-19 impact continues to EPS.
Finally, turning to slide nine now with several years of strong performance and successful track record behind US. We can confidently say we are on a path in approximately the next two years to that important milestone of $500 million in global revenue in one year for gallon sold.
And we lay out those drivers here.
And really the exact timing of this milestone will be dependent on how quickly things return to normal post COVID-19, but we continue to expect to generate $1 billion in cumulative revenue over the next three years, which will contribute.
Bradley L. Campbell: Finally, turning to slide nine, now with several years of strong performance and a successful track record, we can confidently say we are on a path in approximately the next two years to that important milestone of $500 million in Global Revenue in one year for Galifold. And we lay out those drivers here.
Significant amount towards funding, our R&D and opex over that period and.
And we have even further confidence now in that $1 billion peak opportunity as we continue to see significant growth in the fabry market globally, which is driven by continued diagnosis from high risk screening newborn screening and other diagnostic initiatives, which we're investing in as well and.
Jeffrey P. Castelli: And really, the exact timing of this milestone will be dependent on how quickly things return to normal post-COVID, but we continue to expect to generate $1 billion in cumulative revenue over the next three years, which will contribute a significant amount towards funding our R&B and OPEX over that period. And we have even more confidence now in that $1 billion peak opportunity as we continue to see significant growth in the Fabry market globally, which is driven by continued diagnosis from high-risk screening, newborn screening, and other diagnostic initiatives, which we're investing in as well.
And finally, as we have orphan coverage excuse me orphan exclusivity in the us and Europe.
In addition to our 24 Orange book listed patents that give us IP coverage into the late 2000, <unk> 11 of which provide protection through 2038, so lots of.
For two to continue to provide access to <unk> globally for many years to come.
With that let me now hand, the call over to Dr. Jeff <unk>, Who's our Chief Development Officer, Jeff will highlight our Atg, a program and our gene therapy pipeline Jeff.
Thank you Brad and good morning, everyone.
Jeffrey P. Castelli: And finally, as we have orphan coverage, excuse me, orphan exclusivity in the U.S. In Europe, in addition to our 24 orange book listed patents that give us IP coverage into the late 2030s, 11 of which provide protection through 2035. So lots of opportunities to continue to provide access to GALShold globally for many years. With that, let me now hand the call over to Dr. Jessica Steli, who's our chief development officer. Jeff will highlight our ATGA program and our gene therapy pipeline.
Moving onto our R&D updates on slide 11, we wanted to start with <unk>. Our novel next generation therapy for Pompe disease.
Pompei is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders.
With significant unmet need that remains today.
In addition to all of the individual human tragedies.
<unk> seen multiple publications and natural history studies have pumped a patients that highlight the initial benefit of treatment for a few years that US then followed by long term decline on key measures of disease for a majority of patients.
As a reminder, the high unmet need ERP experience population has only ever been studied in a controlled setting in our phase III propel clinical trial with <unk>.
Jeffrey P. Castelli: Thank you, Brad, and good morning, everyone. Moving on to our R&D updates on slide 11, we wanted to start with ATGA, our novel Next Generation Therapy for Pompea disease. Pompeii is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders with significant unmet need that remains today, in addition to all of the individual human tragedies. We've seen multiple publications and natural history studies of Pompeii patients that highlight the initial benefit of treatment for a few years that is then followed by long-term decline on key measures of disease for a majority of patients.
All other control late onset Pompe disease studies have been in participants naive to treatment.
Slide 12 presents a summary of the top line efficacy and biomarker data.
Minder propeller was a double blind randomized study assessing the efficacy and safety of <unk> in adult treatment naive and ERP experience participants against the currently approved therapy.
We enrolled 123 patients at 62 sites in 24 countries.
117 of those patients completed the study and all have voluntarily enrolled in the extension study to continue on atg as their only disease modifying treatment for their pump any disease.
Jeffrey P. Castelli: As a reminder that the high unmet need, ERT experience population has only ever been studied in a controlled setting in our phase three propel clinical trial with ATJA. All other controlled late onset Pompeii disease studies have been in participants naive to treat. Slide 12 presents a summary of the top-line efficacy and biomarker data. As a reminder, Propel was a double-blind, randomized study assessing the efficacy and safety of ATGA in adult, treatment-naive, and ERT-experienced participants against the currently approved therapy.
On the primary endpoint of six minute walk distance patients on a T. J outperformed those on <unk> Alfa in the overall population for the difference between groups of 14 meters, which did not quite reach statistical significance for superiority.
However on the first key secondary endpoint of percent predicted forced vital capacity for SBC in the overall population atg assured us nominally statistically significant and clinically meaningful difference for superiority versus other cost saves alpha with a difference of 3% and a P value of zero point.
Jeffrey P. Castelli: We enrolled 123 patients at 62 sites in 24 countries. 117 of those patients completed the study, and all have voluntarily enrolled in the extension study to continue on ATGA as their only disease-modifying treatment for their Pompeii disease. On the primary endpoint of six-minute walk-dust, patients on ATGA outperformed those on Albuquerada's Alpha in the overall population, with a difference between groups of 14 meters, which did not quite reach statistical significance for superiority.
023.
This is a very impactful finding as progressive loss of pulmonary function is the leading cause of mortality in Pompeii.
And this was the main end point upon which <unk> Alpha was approved.
Here on this slide we group these endpoints into domains of motor function muscle strength pulmonary function patient reported outcomes or PR roads, and Biomarkers and you can see that the totality of data favor a T J over <unk> Alpha and both the overall and <unk> experienced populations.
Jeffrey P. Castelli: However, on the first key secondary endpoint of percent predicted forced vital capacity, or FBC, in the overall population, ATGA showed a nominally statistically significant and clinically meaningful difference for superiority versus Aguacococidase alpha, with a difference of 3% and a p-value of 0.023. This is a very impactful finding as progressive loss of pulmonary function is the leading cause of mortality in Pompeii, and this was the main endpoint upon which Aglicosity's alpha was approved.
We remind everyone that the propel study tested for superiority versus an approved therapy not placebo net the bar for approval for the second generation product typically requires only non inferiority to be shown not superiority for approval.
As shown on our full year call and post hoc non inferiority analysis for the primary endpoint of six minute walk and the first key secondary end point. That's FTC. These non inferiority analysis, we're highly significant.
Moving on now to slide 13, we have our next steps surrounding the development regulatory and manufacturing strategy for the Atg AA program for.
Jeffrey P. Castelli: Here on this slide, we group these endpoints into domains of motor function, muscle strength, pulmonary function, patient-reported outcomes or PROs, and biomarkers. You can see that the totality of the data favors ATGA over Aglococadase Alpha in both the overall and ERT experience population. We remind everyone that the Propel study tested for superiority versus an approved therapy, not placebo, and that the bar for approval of a second-generation product typically requires only non-inferiority to be shown, not superiority for approval. As shown in our full-year call in post hoc non-inferiority analyses for the primary endpoint of the six-minute walk and the first key secondary endpoint of SDC, these non-inferiority analyses were highly significant.
First as John mentioned, our Rolling BLA submission, which was initiated with the FDA in the fourth quarter of 2020 remains on track with the submission of the final module to be completed here in the second quarter of 2021.
Additionally, our MAA submission with the EU is expected to be completed in the second half of this year and we expect additional global filings to follow.
We look forward to expanding our ongoing open label adolescent study in the 12 to 18 year olds living with Pompe disease. This year as well and our clinical study for Pompeii patients with infantile onset disease is expected to begin this year.
And finally in response to the many requests for compassionate use or extended access that we've received for children with infantile onset pompe disease or expanded access programs for both Pompeii infantile patients and adult onset patients have enrolled multiple patients.
Moving on now to slide 15 to briefly highlight our industry, leading portfolio of gene therapies for rare diseases.
Jeffrey P. Castelli: Moving on now to slide 13, we have our next steps surrounding the development, regulatory, and manufacturing strategy for the ATGA program. First, as John mentioned, our rolling BLA submission, which was initiated with the FDA in the fourth quarter of 2020, remains on track with the submission of the final module to be completed here in the second quarter of 2021. Additionally, our MAA submission with the EU is expected to be completed in the second half of this year, and we expect additional global filings to follow.
Several amicus presentations were given at the World Symposium Conference in February of this year, covering our lead gene therapy clinical programs and <unk>, six and <unk> batten disease, respectively day.
Data from both studies continue to show the potential for stabilized disease progression in these children when compared to natural history.
Remain focused on the manufacturing activities and regulatory discussions for both programs to enable dosing of additional patients for the GMP clinical grade material as soon as possible.
On slide 16, we continue to make progress across our preclinical gene therapy programs with Penn and we are excited to share that new data from our <unk> brand Pompeii gene therapy programs will be presented this week at the American Society of gene and cell therapy conference.
Jeffrey P. Castelli: We look forward to expanding our ongoing open-label adolescent study and the 12- to 18-year-olds living with Pompeii disease this year as well. And our clinical study for Pompeii patients with infantile onset disease is expected to begin this year. And finally, in response to the many requests for compassionate use or expanded access that we've received for children with infantile onset Pompeii disease, our expanded access programs for both Pompeii infantile patients and adult onset patients have enrolled multiple patients.
Data from these studies further validate our innovative approach to gene therapy by combining amicus protein engineering expertise with Penn's gene transfer expertise and technologies.
We believe this is just the beginning of untapped the power of this collaboration.
As a reminder, amicus has rights to over 50 diseases under this collaboration including seven currently in active preclinical programs.
With that I would like now to turn the call over to Dr. <unk> to review, our financial results guidance and outlook Daphne.
Jeffrey P. Castelli: Moving on after slide 15, to briefly highlight our industry-leading portfolio of gene therapies for rare diseases, several amicus presentations were given at the World Symposium Conference in February of this year, covering our lead gene therapy clinical programs in CLN6 and CLN3Bat disease, respect. Data from both studies continue to show the potential to stabilize disease progression in these children when compared to natural history.
Thank you, Jeff and good morning, everyone. Our financial overview begins on slide 18, with our income statement for the first quarter ending March 31 2021.
For the quarter, we achieve California's revenue of $66 4 million, which is a 10% increase over the same period last year.
This includes year over year operational revenue growth measured at constant currency exchange rates at 6% and a positive currency impact of 4%.
Jeffrey P. Castelli: We remain focused on the manufacturing activities and regulatory discussions for both programs to enable dosing of additional patients with the GMP clinical grade material as soon as possible. See slide 16. We continue to make progress across our pre-clinical gene therapy programs with Penn, and we are excited to share that new data from our Fabrian Pompeii gene therapy programs will be presented this week at the American Society of Gene and Cell Therapy Conference. Data from these studies further validate our innovative approach to gene therapy by combining Amicus's protein engineering expertise with Penn's gene transfer expertise and technologies.
Total operating expenses were $112 9 million in the first quarter, which is a decrease as compared to 132 million in the first quarter of 2020, primarily driven by the timing of contract manufacturing and research.
On a non-GAAP basis total operating expenses were 95 million in the first quarter as compared to $116 7 million in the first quarter of 2020.
The decrease in research and development cost reflects the timing of investments in our pipeline specifically the timing of manufacturing batches at Apta and research cost, which we expect to incur in subsequent quarters.
Daphne E. Quimi: We believe this is just the beginning of untapping the power of this collaboration. As a reminder, Amicus has rights to over 50 diseases under this collaboration, including seven currently in active preclinical programs. With that, I would like now to turn the call over to Daphne Queenie to review our financial results, guidance, and outlook.
We define non-GAAP operating expense as research and development and SG&A expenses, excluding share based compensation expense.
<unk> fair value of contingent consideration and depreciation.
Net loss for the first quarter of 2021 was $65 7 million for 25 cents per share as compared to a net loss of $88 9 million or <unk> 35 per share for the prior year period.
Daphne E. Quimi: Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 18 with our income statement for the first quarter ending March 31, 2021. For the quarter, we achieved Gallifold revenue of 66.4 million, which is a 10% increase over the same period last year. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 6% and a positive currency impact of 4%.
As of March 31, 2021, we had approximately 266 million shares outstanding.
Turning now to slide 19, with our current cash position, we are on a path for self sustainability without the need for future financing. We have achieved this milestone through our continued revenue growth with counsel as well as driving efficiencies cost savings and careful expense management.
For the third straight year, we expect total non-GAAP operating expenses in 2021 to remain relatively flat as we leverage global commercial infrastructure that is already in place for the apta, a launch and other products in our pipeline, we transition the costs associated with development of <unk>.
Daphne E. Quimi: Total operating expenses were 112.9 million in the first quarter, which is a decrease as compared to 132 million in the first quarter of 2020, primarily driven by the timing of contract manufacturing and research costs. On a non-gap basis, total operating expenses were 90.5 million in the first quarter as compared to 116.7 million in the first quarter of 2020. The decrease in research and development costs reflects the timing of investments in our pipeline, Specifically the timing of manufacturing batches of ATGA and research costs, which we expect to incur in subsequent quarters.
Simple gene therapy programs in our pipeline.
And we maintain financial discipline, while meeting our objectives.
To reiterate all high priority research programs in gene therapy are moving ahead on schedule and we continue to fully support the work with the Wilson lab at Penn.
A few comments about our cash position and 2021 financial guidance.
Cash cash equivalents and marketable securities for $417 4 million at March 31, 2021, compared to $483 3 million at December 31 2020.
We are reiterating our full year <unk> revenue guidance of $300 million to $315 million. In addition to our non-GAAP operating expense guidance of $410 million for $420 million.
Daphne E. Quimi: We define non-gap 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 the first quarter of 2021 was $65.7 million, or 25 cents per share, as compared to a net loss of $88.9 million, or 35 cents per share, for the prior year period. As of March 31, 2021, we had approximately 266 million shares outstanding. Turning now to slide 19, with our current cash position, we are on a path to self-sustainability without the need for future diluted finance.
And with that let me turn the call back to John for closing remarks.
Great, Thanks, Daphne and Jeff Bradley as well and so as you can see we have been relentlessly focused on performance across the business across all programs driven by a global team of passionate entrepreneurs, who have led and will continue to lead us on our patient focused mission.
I am confident that as the world emerges from this global pandemic amicus will emerge even stronger operator, we're happy to take questions.
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 enter back into the queue. If your question has been answered.
Daphne E. Quimi: We have achieved this milestone through our continued revenue growth with Gallowfold, as well as driving efficiencies, cost savings, and careful expense management. For the third straight year, we expect total non-gap operating expenses in 2021 to remain relatively flat, as we leverage global commercial infrastructure that is already in place for the ATGA launch and other products in our pipeline. We transition the costs associated with the development of ATGAA to multiple gene therapy programs in our pipeline, and we maintain financial discipline while meeting our adjustment. To reiterate, all high-priority research programs in gene therapy are moving ahead on schedule, and we continue to fully support the work with the Wilson Lab at Penn, few comments about our cash position and 2021 financial guidance. Cash, Cash Equivalence, and Marketable Security for $4.4 million at March 31, 2021, We are reiterating our full-year Gallifold revenue guidance of $300 million to $315 million.
Just to remove yourself from the queue. Please press the pound key thank you.
Your first question comes from the line of Lee Cooper, All with Cowen Your line is open.
Good morning, guys. Thanks for taking the question I wanted to ask about the recent full approval.
Fabry enzyme.
I ask why.
Was certainly unexpected by me.
But I kept track of free.
Can you.
Walk us through what you know that drove that conversion and also what what that means for galiform either.
Its current promotion or post approval requirements.
Sure It too you know other than what benefit us.
We really don't know so I'll, just remind everybody of the history debt that was the <unk> product was given approval under the accelerated approval framework in 2003.
Then conducted a phase four study that did not meet its primary endpoint, but the drug I think very appropriately continued to be on the market and available for patients and as you saw from incentive fee was a combination of the registry data real world experience largely that led to the conversion from accelerated.
Daphne E. Quimi: in addition to our non-gap operating expense guidance of $410 million to $429.
To full approval.
For Gallup fold, we continue down the path of a phase four confirmatory study, but likewise, we're also.
John Crowley: 420 million. And with that, let me turn the call back to John for closing. Great, thanks, Daphne, Jeff, and Bradley as well. As you can see, we have been relentlessly focused on performance across the business, across all programs, driven by a global team of passionate entrepreneurs who have led and will continue to lead us on our patient-focused mission. I am confident that as the world emerges from this global pandemic, Amicus will emerge even stronger. Operator, we're happy to take questions.
Building a body of evidence through real world evidence as well as registration studies.
I think could also be very supportive down the road of converting gala fold from an accelerated approval to a full approval. So that's always been part of our strategy.
It has no impact whatsoever on Gallup polls and getting it to patients today, we've seen no disruption in the marketplace no disruption with Payors.
From our perspective for patients with amenable variance, who would be suitable for treatment with Gallup poll that said zero impact.
Operator: Ladies and gentlemen, if you have questions, please press the star and then the number one key on your touchstone 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. Thank you. Your first question comes from the line of Rikou Baral with Cohen. Your line is open. Good morning, guys. Thanks for taking the time to answer.
Your next question is from Devine Ahmad with Bank of America for your line is open.
Hi, good morning, Thanks for taking my question.
Just wanted to get a little bit of color on how the quarter for Gallo fold.
It was impacted on the specifics of COVID-19 and if any of the impact that you've seen from COVID-19 in the first quarter has.
Ritu Subhalaksmi Baral: the question. I wanted to ask about the recent full approval of
Improved.
Over what Youre seeing so far this current quarter and maybe this is a question for you know for bad about how you guys get us to your guidance and what level of confidence you have in being able to meet that guidance range for the year. Thank you.
Ritu Subhalaksmi Baral: Fabrazyme by the FDA. It was certainly unexpected by me, and I thought I kept track of these things.
Ritu Subhalaksmi Baral: Can you guys
Ritu Subhalaksmi Baral: Walk us through what you know that drove that conversion.
Ritu Subhalaksmi Baral: Also, what that means for Gallifold, either its current promotion,
John Crowley: its current promotion or post-approval requirements. Sure, Ritu, you know, other than what Sennephi is indicated, we really don't know much.
Sure. Thanks, Devine Bradley I'll, let you feel dose.
Yes, thanks for being so as it relates to.
John Crowley: I'll just remind everybody of the history that that Faberzine product was given approval under the accelerated approval framework in 2003. It then conducted a phase four study that did not meet its primary endpoint, but the drug, I think, very appropriately, continued to be on the market and available for patients. And as you saw from Sennepard, if it was a combination of their registry data and real-world experience, largely that led to the conversion from accelerated to full approval.
Sort of where we are from a COVID-19 perspective, I thought we provided good color on the call and I think importantly.
Some of the metrics that we're following that the number of prescriptions in the United States, which was the highest this months than it's been in any month since before the pandemic and then as well that kind of rolling new patient starts that we provided color on sort of debt.
Net.
Six months was better than the 12 month and now to three months is better than six months. So so that tells us that demand is not just stable, but increasing.
John Crowley: For Gallifold, you know, we continue down the path of a phase four confirmatory study, but likewise, we're also building a body of evidence through real-world evidence, as well as registration studies that I think could also be very supportive down the road of converting Gallifold from an accelerated approval to a full approval. So that's always been part of our strategy.
As we look out into the field. It is still patchy us I know, we all know, but I think there are certainly places where it's starting to look better and we would anticipate that to continue.
Throughout the year and that's why we provided that color that we think the second half of the year.
We'll be we'll see higher new patient starts from the first half that being said, we're very confident in the guidance for your question.
John Crowley: It has had zero impact whatsoever on Gallifold and getting it to patients today. We've seen no disruption in the marketplace, no disruption with payers. And from our perspective, for patients with amenable variants who would be suitable for treatment with Gallifold, it's had zero impact.
Between $303 15.
I think where we ended up in that range will be again dependent on kind of how quickly we things things.
Reside here, but what we see right now is steady growth.
Steady underlying demand and then all of that is supported by the compliance and adherence rates that continue to be over 90%. So so it's a very durable market as well. So we feel really good about where we are our ability to get product to patients and we're very confident in the guidance that we reiterated here today.
Operator: Your next question is from Tazin Amat with Bank of America. The line is open.
Tazeen Ahmad: Hi, good morning. Thanks for taking my question. Just wanted to get a little bit of color on how the quarter for Gallifold was impacted by the specifics of COVID, and if any of the impact that you've seen from COVID in the first quarter has improved over what you're seeing so far this current quarter. And maybe this is a question for, you know, for Brad about how you guys get to your guidance and what level of confidence you have. and being able to meet that guidance range for the year. Thank you. Sure, thanks, Zizene. Bradley, I'll let you field those.
I'll just add thank you Brad I'll, just add disease and in addition to the growth opportunities. The continued demand patient demand and new patient starts to compliance that Bradley highlighted I'll, just reemphasize that reimbursement continues to be excellent as well with near 100% re authorizations in reimbursement in the United States and price.
Holding throughout the other global markets.
Bradley L. Campbell: Yeah, thanks, Zizene. So as relates to sort of where we are from a COVID perspective, I thought we provided good color on the call, and I think important, you know, some of the metrics that were following that, you know, the number of prescriptions in the United States, which was the highest this month than it's been in any month since before the pandemic. And then as well, that kind of rolling new patient starts that we provided color on, you know, sort of the six months was better than the 12 months, and now three months is better than six months.
Your next question is from Kristen <unk> with Cantor Fitzgerald. Your line is open.
Good morning, everybody. Thanks for taking the question I wanted to ask you one on the gene therapy pipeline, which is what criteria is going into place when considering how to prioritize the candidates you have outside of the batten Fabry and Pompe disease franchises and then how are you and your.
<unk> considering items like Trans gene Engineering capsid selection and route of administration, especially since you are one of the few two recently show clinical data.
Bradley L. Campbell: So that tells us that demand is, you know, not just stable but increasing. And I think as we look out into the field, it's still patchy, as we all know, but I think there are certainly places where it's starting to look better, and we would anticipate that to continue throughout the year. And that's why we've provided that color to show that we think the second half of the year will see higher new patient starts than the first half.
Interest equal administration.
Great. Thank you Christian in terms of how we select within our portfolio what I'll go back to the initial decisions on building our portfolio and that was very much based on a disease approach looking at each disease. We again a number of years ago began with a list of nearly 1000 rare diseases we win.
Bradley L. Campbell: That being said, we're very confident in the guidance to your question, between 300 and 315. And I think where we end up in that range will be, again, dependent on kind of how quickly we, things reside here.
Note that down to under 100 and there of course, we looked at the unmet need the technical feasibility of gene therapy broadly, we looked specifically at the technical fit of combining the Penn gene transfer technologies with amicus protein engineering.
Bradley L. Campbell: But what we see right now is steady growth and steady underlying demand. And then all of that is supported by compliance and adherence rates that continue to be over 90%. So it's a very durable market as well. So we feel really good about where we are, our ability to get product to patients, and we're very confident in the guidance that we reiterated here today. I'll just add, thank you, Brad; I'll just add to Zine.
We look at size of patient populations, we looked at availability of natural history, I think all of that competitive dynamics as well and then when we look at our portfolio. Today. If you take for instance for Fabry and Pompe gene therapy programs.
Bradley L. Campbell: In addition to the growth opportunities, the continued demand, patient demand, the new patient starts, and the compliance that Bradley highlighted, I'll just reemphasize that reimbursement continues to be excellent as well, with near 100% reauthorizations and reimbursement in the United States and price holding throughout all the global markets. Your next question is from Christian Cuska with Cancer Fitzgerald. The line is open.
Those continue to be key strategic priorities for amicus, we're moving those forward.
We're moving them as fast as the science and the manufacturing and analytical technologies are allowing and there. If you recall back in November we announced our February drug candidate selection again, combining the amicus in 10 technologies and that was 12 months to 18 months ahead of our original internal projections.
So we had to make.
To make sure that we have the financial capital of the human capital and the manufacturing capacity available, which we did.
Operator: Good morning, everybody. Thanks for taking the question. I wanted to ask you one question on the
Kristen Brianne Kluska: I would ask you one on the gene therapy pipeline, which is what criteria are going into place when considering how to prioritize the candidates you have outside of the Baton, Fabre, and Pompeii disease franchises. And then how are you and your collaborators considering items like trans gene engineering, capsid selection, and route of administration, especially since you are one of the few who recently showed clinical data via intraciecal administration?
By reordering some earlier parts of our priority. So in effect Fabry gene therapy has leapfrogged Pompeii based on technical feasibility and our ability to advance it but within all of those disciplines.
With that Jeff maybe if you can comment on how we think about the different pieces of the technology, including route of administration.
John Crowley: Great, thank you, Chris. And in terms of how we select within our portfolio, I'll go back to the initial decisions on building our portfolio, and that was very much based on a disease approach. Looking at each disease, we again, a number of years ago, began with a list of nearly a thousand rare diseases. We went from that down to under 100.
Sure Hi, Kristen.
So as you pointed out our approach to the gene therapy collaboration with Penn as we rely on our expertise from the protein engineering side really to help optimize cross correction, where does the sales we can trans tiers that those cells can then create the protein and treat other neighboring cells.
You have a whole host of technologies from Penn that we can rely on for the caps for delivery and the route of administration really you know it depends on whether we're trying to address systemic cells and tissues versus trying to get into the CNS, sometimes it's a little bit of both so it's really going to cross that toolbox to find the right <unk> comps for the REIT rather administration.
John Crowley: And there, of course, we looked at the unmet need, the technical feasibility of gene therapy broadly. We looked specifically at the technical fit, of course, combining the pen gene transfer technologies with amicus protein engineering. We looked at the size of patient populations. We looked at the availability of natural history. I think all of that, and competitive dynamics as well.
So that we can.
Really get a first or in this case with Penn really our goal is to get best in class gene therapies. So far we've had great success as we've shown with fabry and Pompe <unk> been finding what we think is the right combination of those key attributes and we have ongoing studies across those preclinical programs right now looking at different combinations of all.
John Crowley: And then when we look at our portfolio today, if you take, for instance, the Febre and the Pompeii gene therapy programs, those continue to be key strategic priorities for amicus. We're moving those forward. We're moving them as fast as science and the manufacturing and analytical technologies are allowing. And there, if you recall, back in November, we announced our February drug candidate selection, again, combining the amicus and Penn technologies. And that was 12 to 18 months ahead of our original internal projections.
Those factors, so we think that debt, having the ability to do so is a great strength for that collaboration.
Your next question is from Amazon <unk> Rama with Jpmorgan. Your line is open.
Good morning, guys.
On the call for us.
Thanks for taking our question.
John Crowley: So we had to make sure that we had the financial capital, the human capital, and the manufacturing capacity available, which we did by reordering some earlier parts of our priority. So, in effect, Fabre gene therapy has leapfrogged Pompeii based on technical feasibility and our ability to advance it within all of those disciplines. Jeff, maybe you can comment on how we think about the different pieces of the technology, including the route of administration. Sure, hi Kristen.
Just wanted to remark on the batten disease programs.
Can you remind us of where you see timelines for dosing additional C. O N six patients with GMP clinical grade material and also similarly for the CLO III program, where are you with respect to manufacturing on MS. Yellen Great program. Thanks, so much.
Yeah of course Tessa. Thank you so really the two key activities for both feeling sick from feeling three have been on the manufacturing both the scale up as well as the production itself and then of course, all the analytical work necessary to support going into patients with not only commercial grade and quality material.
Jeffrey P. Castelli: So as you pointed out, our approach to the gene therapy collaboration with Penn as we rely on our expertise on the protein engineering side really to help optimize cross-correction where the cells we can transuse that those cells can then secrete the protein and treat other neighboring cells. We have a whole host of technologies from Penn that we can rely on for the caps of delivery. And the amount of administration really depends on whether we're trying to address systemic cells and tissues versus trying to get into the CNS. Sometimes it's a little bit of both.
And scale, but also having all the analytical components in place. So we can properly characterize it to support a BLA that's been part of ongoing negotiations and discussions with the FDA. They provided very helpful feedback from a manufacturing standpoint, we're in a really good place and have commenced a GMP manufacturing for both.
Jeffrey P. Castelli: So it's really going across that toolbox to find the right trans gene, the right cap, so the right rather administration so that we can, you know, really get first, or in this case with Penn, really the goal is that they get best in class gene therapies. So far, we've had great success, as we've shown with Fabre and Pompeii, in finding what we think is the right combination of those key attributes.
<unk> six and <unk> three the gating factor is going to be to ensure that we have all of those technical last days tightened up to at the appropriate levels. So that we could go into patients and then of course with not only GMP grade commercial scale material, but as well having the all the analytical assays in place.
Jeffrey P. Castelli: And, you know, we have ongoing studies across those pre-clinical programs right now; you're looking at different combinations of all of those factors. So we think that having the ability to do so is a great strength for that.
Now and again, it's not just us I think you've seen this broadly across the gene therapy field, a tightening of standards.
We saw this coming in the fall of 2019, So I think in many regards we have been quite ahead of the curve.
Operator: Your next question is from Anupon Rama with J.B. Morgan. Your line is open. Good morning, guys. This is Tessa on the call for Anupam. Thanks for taking our question. Just one from us on the bat and disease programs.
Before we received any feedback from the agency we were already planning on for instance, the potency assay ensuring that that was in a very good place as well as the tech transfer to Thermo Fisher Brammer for the GMP manufacture obviously other tech transfer has been completed they have been.
Anupam Rama: Can you remind us of where you see timelines for dosing and
Anupam Rama: additional CLN6 patients with DMP clinical grade material, and also similarly for the CLN3 program. Where are you with respect to manufacturing the CLN3 program?
Some improvements to the manufacturing process, but importantly, they remained at the same scale.
And again, we're in a really good place for their partnership with all the capacity, we have reserved and the technical success, we've had with the Thermo Fisher team.
Jeffrey P. Castelli: on the CLN3 program. Thanks so much.
Your next question is from Celgene, Mr with Goldman Sachs. Your line is open.
Jeffrey P. Castelli: Yeah, of course, Tessa, thank you. So really, the two key activities for both DLN6 and CLN3 have been the manufacturing, both the scale up as well as the production itself. And then, of course, all the analytical work necessary to support going into patients with not only commercial grade and quality material and scale but also having all the analytical components in place so we can properly characterize it to support a BLA. That's been part of ongoing negotiations and discussions with the FDA. They provided very helpful feedback.
Good morning, Thanks for taking my question.
Just elaborate a little bit more on your your past comment here could you just talk about the broader sales out of manufacturing.
As you look at building out that the gene therapy portfolio not just from the extra.
External or with brammer, but maybe whether you are looking to to build internal and internal base.
Manufacturing platform here.
Yeah. Thank you Celgene Bradley do you want to talk about our strategy for gene therapy manufacturing.
Yes, so I mean, it's a great question as you know the first step as we as we moved into this space was to secure.
Jeffrey P. Castelli: From a manufacturing standpoint, we're in a really good place and have commenced GMP manufacturing for both CLN6 and CLN3. The gating factor is going to be to ensure that we have all of those technical assays tightened up at the appropriate levels so that we could go into patients then, of course, with not only GMP-grade commercial scale material but also all the analytical assays. is in place. And again, it's not just us.
We think world class partners to for external manufacturing and we did that with Thermo Fisher Brammer.
We secured our casting supply for for multiple years and have a very flexible arrangement and we're doing a lot of work with our partners at Penn and a number of other collaborators to continue to work on next generation manufacturing platforms, but the good news is for the first part of our portfolio, which is the CNS delivered portfolio there.
Jeffrey P. Castelli: I think you've seen this broadly across the gene therapy field, a tightening of standards. We saw this coming in the fall of 2019, so I think in many respects, we've been quite ahead of the curve. Before we received any feedback from the agency, we were already planning on, you know, for instance, the potency assay ensuring that that was in a very good place, as well as the tech transfer to Thermo Fisher-Brammer for the GMP manufacturer.
Are we as John mentioned in the previous question, we've made great progress in working with Thermo Fisher to be able to support the next studies in <unk> III.
From a medium term perspective, we are actually well underway towards building out our own internal clinical GMP manufacturing facility.
And that facility is state of the art designed to support both to be adherent platform debt that.
That will support our CNS programs, but also have flexibility to support process development for for suspension.
Jeffrey P. Castelli: Obviously, all the tech transfer has been completed. There have been some improvements to the manufacturing process, but importantly, they have remained at the same scale. And again, we're in a really good place with our partnership with all the capacity we've reserved and the technical success we've had with the Thermal Fisher team.
<unk> manufacturing platform as we look towards Pompeii and other systemically delivered gene therapy programs that'll be a really important.
Part of our capabilities and capacity to support our pipeline going forward and in the long term, we think building our own commercial manufacturing could be a strategic assets and.
Operator: Your next question is from Salveen Lytton with Golden Sachs. Your line is open. Good morning. Thanks for taking my time.
And so we would look to do that.
Continue to support the ongoing growth for our gene therapy portfolio.
Salveen Jaswal Richter: Good morning, thanks for taking my question. If you can't just elaborate a little bit more on your past comment here,
Yeah.
Your next question is from Mohit Bansal with Citigroup. Your line is open.
Salveen Jaswal Richter: Could you just talk about the broader build-out of manufacturing as you look to build out the gene therapy portfolio, not just from the, you know, external work with the Brammer but maybe whether you're looking to build an internal-based manufacturing platform here? Yeah, thank you, Selvine. Bradley, do you want to talk about our strategy for gene therapy manufacturing? Yeah, Salvin, it's a great question.
Great. Thanks for taking my question.
Congrats on your talking by FDA regarding ACTH.
Maybe a question Big picture question on gene therapy.
Last year was in the last 12 months or so we have seen a lot.
Challenges for our gene therapy programs.
The regulatory or even from <unk> safety point of view, so did that in mind give us debt.
Bradley L. Campbell: As you know, the first step as we moved into this space was to secure, we think, world-class partners for external manufacturing. We did that with Thermo Fisher-Bramer. We secured our caps and supplies for multiple years and have a very flexible arrangement, and we're doing a lot of work with our partners at Penn and a number of other collaborators to continue to work on next-generation manufacturing platforms. But the good news is for the first part of our portfolio, which is the CNS delivered portfolio.
At the cusp of entering into clinics it bumped integrity.
What is your updated understanding in terms of magnitude of cloud I mean, it does seem like the FDA is little bit more.
Cautious about disease, there is an existing drug out debt and also from the safety and efficacy point of view, what's the Bod and how you are deciding on which credit which drove for diseases to go up.
Bradley L. Campbell: There, as John, I think, mentioned in the previous question, we've made great progress in working with Thermo Fisher to be able to support the next studies in CLN6 and CLN3. From a medium-term perspective, we're actually well underway toward building out our own internal clinical GMP manufacturing facility. And that facility is state-of-the-art designed to support both the adherent platform that will support our CNS programs but also have the flexibility to support process development for suspension-based manufacturing platforms as we look towards Pompeii and other systemically delivered gene therapy programs.
Thank you.
Yeah. Thanks for the Big Picture question Mohit I think it is a very important one.
When we came into the world of gene therapy for amicus. It really was an evolution building on our experience in genetic medicine with Gallup fold with biologic development.
Plex biologic manufacturing with 80, GAA and then also our experience in the broad global regulatory.
Paradigm, what we wanted to make sure that we not only selected the appropriate diseases, but we brought the right technologies to bear we.
Like Jim Wilson were very strongly of the view that high dose systemic AAV delivery was not appropriate in fact could actually be quite dangerous for patients. So part of the thesis of the collaboration between U Penn in Amicus was again that we can we need to be mindful of the protein that's.
Bradley L. Campbell: That will be a really important part of our capability and capacity to support our pipeline going forward. And in the long term, we think building our own commercial manufacturing could be a strategic asset. And so we would look to do that to continue to support the ongoing growth of our gene therapy portfolio.
Being expressed by the gene therapy vectors in technologies. So if we at amicus can engineer the appropriate trans genes again customized to each disease area to each molecule. So for instance in February with a focus on stability and plasma as well as targeting in Pompeii a focus on targeting.
Operator: Your next question is from Mohit Van Sal with Citigroup. Your line is open.
Mohit Van Sal: Great, thanks for taking my question and congrats on your talk about it.
Mohit Van Sal: by MTA regarding APA. Maybe a question, a big picture question on gene therapy, so large
Mohit Van Sal: Within the last 12 months or so, we have seen a lot of challenges for
Mohit Van Sal: gene therapy programs, be regulatory or even from an efficacy and safety point of view. So with that in mind, given that you are at the cost
Youre, not just transfected liver cells and.
Hoping to get lots of expression that eventually gets taken up we think that could be.
Mohit Van Sal: of entering into clinics with Pompe and Fabry. What is your updated understanding in terms of regulatory requirements? It does seem like that
Not the most efficacious and potentially in.
And unsafe way to deliver gene therapy, what we wanted to do was to combine the technologies from the two organizations to enhance efficacy.
Mohit Van Sal: FTA is a little bit more cautious about this.
Mohit Van Sal: diseases where there is an existing drug out there? And also, from the safety and efficacy point of view, what's the bar and how are you deciding on which drugs or diseases to go out? Yeah, thanks for the big picture question, Moit.
And potentially to enhance safety all the while being mindful of manufacture ability and I think February is an excellent example, where we think we have a very unique molecule with very distinct preclinical data that could potentially be very efficacious very safe and actually could be manufactured at a reasonably small scale.
John Crowley: I think it's a very important one. You know, when we came into the world of gene therapy for amicus, it really was an evolution, building on our experience in genetic medicine with Gallifold, with biologic development, and complex biologic manufacturing with ATGAA, and then also our experience in the broad global regulatory paradigm. What we wanted to make sure was that we not only selected the appropriate diseases, but we brought the right technologies to bear. We, like Jim Wilson, were very strongly of the view that high-dose systemic AAV delivery was not appropriate.
Which of course gives us lots of advantage in terms of investment needed to bring it to market.
Intimately, where the price points, where flexibility we may have there I'll just comment briefly on the regulatory paradigm I will tell you that continues to evolve. It is a very different world and we started to see this change in mid 2019 through the second half of 2019 I think the agency was preparing to provide substantial guidance.
John Crowley: In fact, could actually be quite dangerous for patients. So part of the thesis of the collaboration between UPenn and Amicus was, again, that we need to be mindful of the protein that's being expressed by the gene therapy vectors and technologies. So if we at Amicus can engineer the appropriate trans genes, again, customized to each disease area, to each molecule.
To gene therapy developers throughout 2020.
They did to the extent that they had capacity too but of course seeber was significantly overwhelmed by the COVID-19 crisis. So I think that's taken longer to develop we really were with our core technologies and strategic approach and I think forward looking to the regulatory paradigm that was changing.
John Crowley: So, for instance, in February, a focus on stability in plasma as well as targeting. In Pompeii, a focus on targeting, so that you're not just transfecting liver cells and hoping to get lots of expression that eventually gets taken up. We think that could be not the most efficacious way to deliver gene therapy.
You'll see that we'll be in a very very unique place with respect to both February and from PE and other.
Systemic delivery programs that we have in development and then I'll, just maybe conclude that with the CNS delivery programs a lot of the challenges that we've seen on safety and targeting of sales on delivery and manufacturing with the CNS programs, we have they inherently.
John Crowley: What we wanted to do was to combine the technologies from the two organizations to enhance efficacy and potentially enhance safety all the while being mindful of manufacturability. And I think February is an excellent example where we think we have a very unique molecule with very distinct preclinical data that could potentially be very efficacious, very safe, and actually could be manufactured at a reasonably small scale, which of course gives us lots of advantages in terms of investment needed to bring it to both the market and ultimately, where the price points are the flexibility we may have there.
Think are better advantaged in terms of the technical feasibility of addressing each of those and I think that's reflected in the success, including the safety that we've seen for both our steel and three in sealing six programs.
So you asked a big question, so you've got a big answer.
Your next question is from Doug <unk> with Stifel. Your line is open.
Good morning, guys. Thanks for taking the question and congrats on the quarter I guess.
Two quick clarification questions from us on the <unk> side, John So with regards to the eye.
John Crowley: I'll just comment briefly on the regulatory paradigm. I will tell you that it continues to evolve. It is a very different world.
For the Atg filing can.
John Crowley: And we started to see this change in mid-2019 through the second half of 2019. I think the agency was preparing to provide substantial guidance to gene therapy developers throughout 2020. They did to the extent that they had the capacity to, but, of course, Cibre was significantly overwhelmed by the COVID crisis. So I think that's taken longer to develop. We really were with our core technologies and strategic approach, and I think forward to the regulatory paradigm that was changing.
Can you remind us where the manufacturing sites are for that drug material and secondly, it's very basic question and forgive me, if it's too basic but.
Now that you are dealing with a modified T. That's somewhat recognized as an approved drug and Youre also using Nicholas debt does the combination approach that you're employing in atg, a warrant an AD com. Thank you.
Great. Thanks, Dagon with respect to a T. J a again, we think we're in a very good place from a CMC perspective that'll be one of the final parts of the BLA. The manufacturing currently is in Wuxi biologics facility in Wuxi, that's already been inspected by FDA.
John Crowley: I think we'll see that we are in a very, very unique place with respect to both February and Pompeii and other systemic delivery programs that we have in development. And then I'll just maybe conclude that with the CNS delivery programs, a lot of the challenges that we've seen on safety, on targeting of cells, on delivery, on manufacturing. With the CNS programs we have, they inherently, I think, are better-advantaged in terms of the technical feasibility of addressing each of those. And I think that's reflected in the success, including the safety, that we've seen for both our CLN3 and CLN6 programs.
Previously undergone.
Inspections.
We are also in the final stages of constructing a large commercial facility outside of Dublin in Ireland and that will come online next year and that will increasingly be an important part of the commercial supply. So early on we see a dual supply both China and Ireland, providing that product with respect.
To our having both an E R T and a chaperone component of course that does and we've stated this along the way this will require both a BLA and an NDA and.
John Crowley: You asked a big question, so you got a big answer.
Operator: Your next question is from Daigonha; with Cepo, the line is open.
Dae Gon Ha: Good morning, guys. Thanks for taking the question and congratulations on the quarter. I guess we have two quick clarification questions from us on the ATGA side, John. So with regard to the, I guess, for the ATGA filing, can you remind us where the manufacturing sites are for that drug material? And secondly, it's a very basic question, and forgive me if it's too basic. But Now that you're dealing with a modified ERT that's somewhat recognized as an approved drug, and you're also using MIGLostat, does the combination approach that you're employing in ATGA warrant an adcom? Thank you.
And we have no indication whatsoever that that would lead necessarily to an outcome.
Your next question is from Joseph Schwartz with SBB Leerink. Your line is open.
Great. Thanks, very much Hello, amicus team I was wondering if you could expand a little bit on the.
The other.
The topics that were discussed at the pre BLA meeting, where there any in particular that.
Seem to be.
More derisked than others any review issues.
That you think the FDA might be.
John Crowley: Great, thanks, Dagon. With respect to ATGA, again, we think we're in a very good place from a CMC perspective. That'll be one of the final parts of the BLA. The manufacturing currently is in Wushi Biologics' facility in Wushi that's already been inspected by FDA and has previously undergone PAI inspections. They are also in the final stages of constructing a large commercial facility outside of Dublin in Ireland. And that will come online next year, and that will increasingly be an important part of the commercial supply.
Still have.
To grapple with.
And then what do you need a pre NDA meeting just two.
Clarify based on the.
The last comments that you just made about both components of the T. G I.
Sure. Thanks, Joe I just on that the answer is no we don't need a pre NDA meeting one meeting suffice to cover both the large and the small molecule I'll just comment that the meeting itself was excellent and tone. It was collaborative provided us all the feedback we needed to ensure that we have the strongest submission with.
John Crowley: So early on, we see a dual supply, with both China and Ireland providing that product. With respect to our having both an ERT and a chaperone component, of course, that does, and we've stated this along the way, this will require both a BLA and an NDA, and we have no indication whatsoever that that would lead necessarily to an adcom.
With respect to or will there be review issues I'm sure there will be I've never known a BLA that didn't have review issues. So I think yes, but we feel very confident that the data package. We have together with the breakthrough therapy designation certainly the unmet need in the community.
And again, we can I think this was a really important step forward, having this formal pre BLA meeting receiving the written minutes being aligned with the FDA on the BLA submission and again that submission will go into the FDA by the end of June.
Operator: Your next question is from Joseph Schwartz with SVB Loring. Your lines are open.
Joseph Patrick Schwartz: Great, thanks very much. Hello, Amicus team. I was wondering if you could expand a little bit on the topics that were discussed at the pre-BLA meeting. Were there any in particular that seemed to be more de-risk than others, any review issues that you think the FDA might still have to grapple with? And then, will you need a pre-NDA meeting just to clarify based on the last comments that you just made about both components of the ATGA? Sure, thanks, too.
And.
Fully prepared to bring that product to as many patients as quickly as possible.
Your next question is from.
Chip.
Hi, Julien.
Hi.
Hi.
Hi, Good morning team. This is Robert on for Doug. Thanks.
John Crowley: Sure, thanks, Joe. But just on that, the answer is no.
Thanks for taking our call.
My question today is around helicopter.
John Crowley: We don't need a pre-NDA meeting, but one meeting suffices to cover both the large and the small molecule. I'll just comment that the meeting itself was excellent in tone. It was collaborative.
<unk> on first pass approval for <unk>.
And if you've had any feedback from the EMA when a potential MMA submission with existing notice it.
Thank you.
Yeah. Thanks, Robert I'll, just say that we are continue to be highly confident in atg aaas at prove ability and with respect to the MAA. We're already engaged with the MAA the authorities and we're on track on our timeline for submission in the second half of 2021.
John Crowley: It provided us with all the feedback we needed to ensure that we had the strongest submission. With respect to, will there be review issues? I'm sure there will be. I've never known a BLA that didn't have review issues.
John Crowley: So I think yes, but we feel very confident that the data package we have, together with the breakthrough therapy designation, certainly addresses an unmet need in the community. And again, we can say, I think this was a really important step forward, having this formal pre-BLA meeting, receiving the written minutes, being aligned with the FDA on the BLA submission. And again, that submission will go to the FDA by the end of June, and we're fully prepared to bring that product to as many patients as quickly as possible.
We have a follow up question from Michael Brown with Cowen Your line is open.
Hi, Thanks, guys I'll make us pretty quick.
John You mentioned that the adolescent study is ongoing.
And that you plan on starting the infantile study soon can you I guess one.
Give us an update on when that adolescent data might generate first.
The first efficacy data I guess.
Operator: Your next question is from the Guttapad Hyde with Jukin-Hanelan.
For perspective, I'm wondering if it is.
Guttapad Hyde: Hi, good morning team. This is Robert on Ford Degget.
Is it might generate.
You can see data during the review cycle at the original BLA.
Guttapad Hyde: Thanks for taking our call. My question today is around how confident the team is on first-pass approval for ATGAA. And if you've had any feedback from the EMA on a potential MNA submission with the existing data set, thank you.
And if it might constitute a.
Supplemental submission.
And then just the design of the infantile study as Youre thinking about it.
John Crowley: Yeah, thanks, Robert. I'll just say that we continue to be highly confident in ATGA's approvability, and with respect to the MAA, we're already engaged with the MAA, and the authorities, and we're on track and on our timeline for submission in the second half of 2021.
This year thanks.
Sure It too of course, the adolescent study we had begun enrolling last year. It was the one clinical program at amicus, where we did see that.
Fective COVID-19 in delaying or deferring some enrollment.
So we'll see a pickup in enrollment is a reasonably small study.
Operator: We have a follow-up question from Rikou Barang with Cohen. The line is open.
Likely that we will get all the data from that during the review period. So I think that will come just after what we would expect to be the approval of Atg I E. In the late onset pompe disease population, so likely the expansion of the label would be part of the I think a relatively straightforward S supplemental BLA submission.
Ritu Subhalaksmi Baral: Hi, thanks guys. I'll make this pretty quick. John, you mentioned that the adolescence study is ongoing and that you plan on starting the infantile study soon. Can you
Ritu Subhalaksmi Baral: I guess one, give us an update on when that adolescent data might generate first efficacy data. I guess, for perspective, I'm wondering.
In the infantile study again, we're not yet prepared to disclose that.
John Crowley: For perspective, I'm wondering if it might generate efficacy data during the review cycle of the original BLA, and if it might constitute a supplemental submission, and then just the design of the infantile study as you're thinking about it, start this year. Sure, Ritu, and of course, the adolescent study we had begun enrolling last year. It was the one clinical program at Amicus where we did see an effective COVID in delaying or deferring some enrollment.
Full nature of that study, but it'll be reasonably small.
It will not be a controlled studies. So nobody will have to go to we don't believe believe certainly not to a placebo or to a competitive product and that will continue to evaluate key star.
<unk> started that steady here over the next couple of months, but we expect it to start in the next quarter or two and I'll just remind everybody that.
John Crowley: So we'll see a pickup in enrollment as a reasonably small study, but it's unlikely that we'll get all the data from that during the review period. So I think that'll come just after what we would expect to be the approval of ATGA and the late-onset Pompeii disease population. So, likely, the expansion of the label would be part of what I think would be a relatively straightforward S supplemental BLA submission. In the infantile study, again, we're not yet prepared to disclose the full nature of that study, but it'll be reasonably small.
It's a very important part of the pump a population. That's also a very very small part relatively of the pompe population, but very important that we study it and I'll remind people also too that we already have treated a number of infants under our expanded access or compassionate use protocol and we will expect actually to have that day.
Yeah.
On a rolling basis, just to provide some more color of the.
The effect under the expanded access protocol, if the medicine on infants.
There are no further questions at this time I would now like to turn the conference back to Mr. John Crowley, Chairman and CEO for closing remarks.
John Crowley: It will not be a controlled study, so nobody will have to go to, we don't believe, certainly not to a placebo or to a competitive product, and we'll continue to evaluate the start of that study here over the next couple of months, but we expect it to start in the next quarter or two. And I'll just remind everybody that it's a very important part of the Pompeii population. It's also a very, very small part, relatively speaking, of the Pompeii population, but very important that we study it.
Great. Thank you everybody for listening thinks that all the analysts for the excellent questions.
Again, very important quarter for us in Q1, and Q2, we see an equally important quarter for us as we move forward on our mission. This year. So thanks, everybody have a great day.
Ladies and gentlemen, this concludes today's conference call. Thank you and have a great day.
John Crowley: And I'll remind people also, too, that we already have treated a number of infants under our expanded access or compassionate use protocol. And we will expect actually to have that data on a... on a rolling basis just to provide some more color of the effect of the medicine under the expanded access protocol of the medicine on infants.
Okay.
John.
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Operator: There are no further questions. At this time, I would like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks.
Good day.
For the game.
Good day.
Yes.
John Crowley: Great, thank you, everybody, for listening. Thanks to all the analysts for the excellent questions. Again, a very important quarter for us in Q1 and Q2. We see an equally important quarter for us as we move forward on our mission this year. So, thanks, everybody. Have a great day.
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Okay.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you, and have a great day.
Okay.
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Operator: Bhopin'i, and so on the way, and so on the end. I'm gonna go. Thank you. Thank you.