Q2 2019 Earnings Call

Operator: Good day, ladies and gentlemen, and thank you for your patience. You've joined the PTC Therapeutics Second Quarter Corporate Updates and Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will be given at that time. Should you require any additional assistance during the call, please press star, then zero on your touchtone telephone.

You've joined the PTC Therapeutics second quarter, corporate update and financial results Conference call.

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

Later, we will conduct a question and answer session and instructions will be given at that time.

Should you require any additional assistance during the call. Please press Star then zero on your Touchtone telephone.

Operator: As a reminder, this conference may be recorded. I would now like to turn the call over to your host, Chief of Staff to the CEO, Timothy Dyer. Sir, you may begin.

As a reminder, this conference maybe recorded.

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

Chief of staff to the CEO Timothy Dyer, Sir you may begin.

Timothy Dyer: Hello, good afternoon, and thank you for joining us to discuss our 2019 second quarter corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcio Souza, and our Chief Financial Officer, Emily Hill. Before we start, let me remind you that today's call will include forward-looking statements based on current expectations. Please take a moment to review our slide on our simultaneous presentation, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements, as any and all such risks can materially and adversely affect our business and results of operations. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP and non-GAAP financial measures and a reconciliation of GAAP and non-GAAP financial measures is available in today's earnings release. With that said, let me pass the call over to our CEO, Stuart Peltz.

Hello, Good afternoon, and thank you for joining us to discuss our 2019 second quarter corporate updates and financial results.

Joining me on today's call is our CEO Stuart Peltz, our Chief operating Officer, Marcio, Sousa, and our Chief Financial Officer, and Lee Hill.

Before we start let me remind you that today's call will include forward looking statements based on current expectations. Please take a moment to review our slide on our simultaneous presentation, which contains our forward looking statements.

Our actual results could materially differ from these forward looking statements as any and such risks can materially and adversely affect our business and results of operation.

For a detailed description of applicable risks and uncertainties. We encourage you to review the Companys. Most recent quarterly report on Form 10-Q , and annual report on Form 10-K filed with the Securities and Exchange Commission as well as the company's other SEC filings.

We will disclose certain non-GAAP information during this call information regarding our use of GAAP and non-GAAP financial measures and a reconciliation of GAAP to non-GAAP is available in today's earnings release with that let me pass the call over to our CEO Stuart Peltz.

Stuart Peltz: Thanks, Tim. And thank you all for joining the call this afternoon. In the second quarter, we've made important progress growing the DMD franchise around the globe. In addition, we have increased the franchise value this quarter by expanding the Enflaga label to include 2- to 5-year-old patients. Furthermore, following approval of TransLarna in Brazil, we completed an annual contract with the Ministry of Health to provide TransLarna to patients. We continue advancing the therapies in our pipeline, with two programs on track to be submitted to regulatory authorities by the end of the year, including an NDA for RISDA plan, a small molecule identified from our splicing platform, and a BLA for our first gene therapy product for the treatment of AADC de Moving these clinical programs to commercial-stage products reflects our continued execution of the five-year strategic plan that we described last year.

Thanks, Tim and thank you all for joining the call. This afternoon.

Over the second quarter, we made important progress growing the DMD franchises around the globe. In addition, we have increased the franchise value. This corner by expanding the implausible label to include two to five year old patient.

Furthermore, following approval of Translarna in Brazil, we completed an annual contract with the Ministry of health to provide translarna to patients.

We continue advancing the therapies in our pipeline with two program is on track to be submitted to regulatory authorities by the end of the year, including the NDA for Rins. The plan of small molecule identified from our splicing platform and ability for our first gene therapy product for the treatment of a DC deficiency.

Moving these clinical programs to commercial stage products reflect our continued execution of the five year strategic plan that we described last year. This vision elucidate ptcs mission of bringing differentiated therapies to patients suffering from rare disorders with limited or no treatment options.

Stuart Peltz: This vision elucidates PTC's mission of bringing differentiated therapies to patients suffering from rare disorders with limited or no treatment options. By fulfilling this mission, we will be creating value for all of our stakeholders. One key pillar of our strategic plan is to continue to build a robust, diversified orphan drug franchise. We believe that one of PTC's key differentiators is our ability to work across multiple scientific platforms to bring orphan products to patients in need of new treatment. Our products and innovative programs currently span across five core platforms, including non-sense mutation read-through, alternative splicing, gene therapy, anti-sense DNA technology, and oncology. We intentionally sought to develop products against targets with differentiated mechanisms of action that allow us to diversify our pipeline, ensuring that we bring innovative products to patients with high medical needs. I'm very proud of the team's execution of the strategic plan. Because of these efforts, we are now in a position to have four product launches over the next year.

By fulfilling this mission, we will be creating value for all of our stakeholders.

Our one key pillar of our strategic plan is to continue to build a robust diversified orphan drug franchise. We believe that one of Ptcs key differentiators is our ability to work across multiple scientific platforms to bring orphan products to patients in need of new treatment.

Our products and innovative programs currently spanned across five core platforms, including nonsense mutation read through alternative splicing gene therapy, antisense DNA technology and on oncology.

We intentionally sought to develop products against targets with differentiated mechanism of action that allow us to diversify our pipeline ensuring that we bring innovative products to patients with high unmet medical need.

Im very proud of the team's execution of the strategic plan because of these efforts. We are now in the position to have for product launches over the next year.

Operator: The air.

Right is the plan for us on May Tech savvy for AJ TTR re lever for FCF and our gene therapy product for a DC deficiency.

Stuart Peltz: RISDA Plan for SMA, TXETI for HATTR, Ray Lever for FCS, and our Gene Therapy Product for AADC Deficiency. In addition, there's potential for U.S. approval of TransLarna for DMD in 2020 based on the outcome of the dystrophin study. The combined potential revenue and royalty streams of these products, all of which are either already approved or will be submitted for approval this year, are anticipated to grow in excess of $1.5 billion in potential revenues by 2023. Our growing commercial infrastructure was strengthened during the second quarter.

In addition, there is potential for us approval of Translarna for DMD in 2020 based on the outcome of the dystrophin study the combined potential revenue and royalty streams of these products all of which are either already approved or will be submitted for approval. This year is anticipated to grow in excess of $1.5 billion in potential revenues by 2023.

Our growing commercial infrastructure was strengthened over the second quarter.

Stuart Peltz: Importantly, we have started to see early access sales of TXETI in Latin America, bringing patients the benefit of in-home injections to treat polyneuropathic HATTR. Because this rare disorder has a Portuguese ancestry, Brazil is one of the largest markets with an estimated 5,000 patients. We know from market research that these patients have a high degree of unmet medical needs, and TXETI offers important therapeutic benefits. To bring treatment to patients as quickly as possible, we have submitted the application for TxETI registration in Brazil and expect to receive it by the end of the year. We also made significant progress in Brazil for TransLarna. As I mentioned on the last call, TransLarna received regulatory approval in Brazil in the second quarter for non-susceptation DMD patients over five years of age.

Importantly, we have started to see early access sales of tech savvy in Latin America, bringing patients the benefit of in home injections to treat poly neuropathic ha.

Because this rare disorder has a Portuguese ancestry, Brazil is one of the largest markets with an estimated 5000 patients. We know from market research. These patients have a high degree of unmet medical need and takes steady offers important therapeutic benefit.

To bring therapy to patients as quickly as possible. We have submitted the application for tech savvy registration in Brazil, and expect to receive this by the end of the year.

We also made significant progress in Brazil for Translarna.

As I mentioned on the last call Translarna receive regulatory approval in Brazil in the second quarter for nonsense mutation DMD patients over five years of age.

Stuart Peltz: Having received the approval, we have now completed our negotiations for an annual contract to sell directly to the Brazilian Ministry of Health. This contract and the INVISA approval will allow for broader patient access in Brazil. As I mentioned earlier, we also expanded in-plaza access to patients in the second quarter. The FDA granted our in-plaza label expansion for patients 2 to 5 years old. This is critical, as treating patients earlier can preserve muscle mass and delay loss of ambulation. Multiple publications from clinical studies, as well as long-term natural history data, show that Inflaza is the superior product compared to prednisone. Our DMD franchise continues to produce robust revenues and provides a strong base in which we are continuing to grow the business. We are reporting that DMD franchise revenue was approximately $85 million in the second quarter. We remain confident in our DMD revenue guidance of $285 to $305 million for full year 2019.

Having received the approval we have now completed our negotiations for an annual contract to sell directly to Brazilian Ministry of health.

This contract and the in visa approval will allow for broader patient access in Brazil.

As I mentioned earlier, we also expanded in plaza access to patients in the second quarter.

The FDA granted our and FLOSEAL label expansion for patients two to five years old. This is critical as treating patients earlier can preserve muscle mass and delay loss of ambulation.

Multiple publications from clinical studies as well as long term natural history data showed that in Florida is the superior product compared to present a zone.

Our DMD franchise continues to produce robust revenues and provides a strong base in which we are continuing to grow the business.

We are reporting that the DMD franchise revenue was approximately $85 million in the second quarter, we remain confident in our DMD revenue guidance of $285 million to $305 million for full year 2019.

The teams have also been working hard to advance our clinical programs, we have been preparing the BLA for our gene therapy product to treat a DC deficiency and are on track to submit the BLM. This year with a potential approval next year.

Stuart Peltz: The teams have also been working hard to advance our clinical programs. We have been preparing the BLA for our gene therapy product to treat AADC deficiency and are on track to submit the BLA this year with a potential approval next year. We are also excited to report that Roche expects the RISDPLAN NDA to be submitted by the end of the year. Roche oversees the RISDPLAN project, and we are supporting this effort. RISDPLAN results were showcased at two medical meetings this quarter, the American Academy of Neurology meeting and the Cure SMA meeting. KOL feedback was overwhelmingly positive, with increasing support for the need for an oral therapy with ease of administration and broad tissue distribution.

We're also excited to report that Roche expects the risk the plan and da to be submitted by the end of the year.

Roche overseas the revised plan, India, and we are supporting this effort.

Risk the plan results were showcased at two medical meetings this quarter.

The American Academy of Neurology meeting and the cure some HBV.

K. oil feedback was overwhelmingly positive with increasing support for the need of an oral therapy with ease of administration and broad tissue distribution.

Unknown Executive: We believe RISDAPlant will be the most competitive therapy in the SMA space. The SMA program was the first project demonstrating that small molecules targeting the splicing apparatus to modulate gene expression can selectively and specifically change the course of disease progression. We are leaders in the small-molecule splicing modulator field. Discovering the first small-molecule drug to affect SMA splicing that will be submitted to the FDA for approval is something that we are all proud of accomplishing. It is an important achievement.

We believe is the plan will be the most competitive therapy in the SDMA space.

We estimate program was the first project demonstrating that small molecule targeting the splicing apparatus to Modularly gene expression can selectively as specifically changed the course of disease progression. We are the leaders of the small molecule spicing modulator field.

Discovering the first small molecule drug to affect SMS splicing that will be submitted to the FDA for approval is something that we are all proud of accomplishing.

It is an important achievement.

Unknown Executive: We have also investigated RISDAPlan's mechanism of action, which has been productive and incredibly valuable. We have synthesized these acti- peptides to create a splicing platform that we have utilized to discover other potential small-molecule splicing modulators to treat diseases. Moving forward, we intend to substantially increase our focus on the splicing platform with the objective of generating several new transformational therapies for patients. Our unique understanding of the splicing mechanism and how it can be modulated by small molecules is a key competitive advantage that we are working hard to continuously improve. We have already produced another candidate within the platform for familial dysautonomia, or FD for short, which is expected to enter the clinic soon, and we anticipate entering the clinic next year for Huntington's disease.

We have also investigated risk the plans mechanism of action, which has been productive an incredibly valuable.

We have to synthesize these efforts to create a splicing platform that we have utilized to discover other potential small molecule splicing modulators to treat diseases.

Moving forward, we intend to substantially increase our focus on the splicing platform with the objective to generate several new transformational therapies for patients.

Our unique understanding of the splicing mechanism and how it can be modulated by small molecules is a key competitive advantage that we are working hard to continuously improve.

We have already produced another candidate within the platform for familial disorder, noemi or ft for short, which is expected to enter the clinic soon and we anticipate entering the clinic next year for Huntingtons disease, but the work does not end there and we intend to generate a significant number of drug candidates using the splicing platform in the coming years.

Unknown Executive: But the work does not end there, and we intend to generate a significant number of drug candidates using the splicing platform in the coming years. Splicing modulation is expected to be a key source of innovation and value for all our stakeholders. Like RISDA plans, both the FD and HD molecules have the potential to demonstrate rapid changes in RNA and protein levels in the blood and other tissues, allowing the ability to show an early proof of concept next year. You may recall that for the SMA molecules, we showed that increases in protein levels were observed in the blood and reflected its clinical activity in the CNS.

Splicing modulation is expected to be a key source of innovation and value for all our stakeholders.

Like Richard the plan, but the ft and HD molecules has the potential to demonstrate rapid changes in R&D and protein levels in the blood and other tissue, allowing the ability to show in early proof of concept next year.

You may recall that for the Essar may molecules, we showed that increases of protein levels were observed in the blood and reflected its clinical activity in the CNS.

Let me turn now to another strategic priority for PTC, our gene therapy platform.

Marcio Souza: Let me turn now to another strategic priority for PTC, our gene therapy platform. Aligned with our strategic imperative to advance the gene therapy portfolio and infrastructure, we are proud to report that PTC has signed a long-term lease agreement with Bristol Myers Squibb Company, under which we gain access to approximately 185,000 square feet of space. This includes an existing state-of-the-art biologics production facility and supporting research and operations buildings on the BMS campus in Hopewell, New Jersey. We plan to further develop the biologics facility to support gene therapy production and also plan to move our research operations to a newly renovated building on the same campus. The buildings we are leasing are located on an existing BMS property of over a million square feet, which is being transitioned to a multi-tenant research and development campus.

Aligned with our strategic imperative to advance the gene therapy portfolio and infrastructure. We are proud to report that PTC has signed a long term lease agreement with Bristol Myers Squibb company under which we gain access to approximately 185000 square feet of space.

This includes an existing state of the art biologics production facility and supporting research and operations buildings on the BMS campus in Hopewell New Jersey.

We plan to further develop the biologics facility to support gene therapy production and also plan to move our research operations to a newly renovated building on the same campus.

The buildings. We are leasing are located on an existing BMS property over a million square feet, which is being transitions to a multi tenant research and development campus.

Marcio Souza: The existing GMP suites on the site were recently renovated and will be used to produce material to serve multiple preclinical and clinical gene therapy programs. This adds to our current preclinical production capacity in Bridgewater, New Jersey. These efforts underscore our commitment to our internal gene therapy program. I'll now turn the call over to our COO, Marcio Sousa, to discuss the details of our commercial and clinical progress.

The existing GMP suites on the site, where recently renovated and will be used to produce material to serve multiple preclinical and clinical gene therapy program. This adds to our current preclinical production capacity in Bridgewater, New Jersey. These efforts underscore our commitment to our internal gene therapy program.

I'll now turn the call over to our COO Marcio Sousa to discuss the details of our commercial and clinical progress Marcio.

Marcio Souza: Hey, thanks, Stu. We're very excited about the results in the first half of the year and remain confident about the full year performance. I'd like to start by reviewing some of the key business dynamics for our commercial portfolio. So far, 2019 has been the strongest commercial performance in the history of PTC.

Hi, Thanks to.

We're very excited with the results in the first half of the and remain cautious stance about the full year performance.

I would like to start by reviewing some of the key business dynamics for our commercial portfolio.

So far 2019 has been the strongest commercial performance in the history of PTC.

It's especially humbling should lead to position off delivering four distinct therapy for rare disorders, all with high medical unmet needs.

Marcio Souza: It's especially humbling to be in the position of delivering four distinct therapies for rare disorders, all with high medical unmet needs. We are proud to be delivering differentiated therapies for thousands of patients globally. Let me start by reviewing MFLAZA, the only treatment approved in the United States for all DMT patients older than 2 years of age.

We are proud to be delivering differentiated therapies.

For thousands of patients globally.

Let me start by reviewing and Plaza.

The only treatment approved in the United States for all DMD patients older than two years of age.

The non Florida, Florida continues to grow and you have seen compliance of patients on drug around 90%.

Marcio Souza: Demand for emplaza continues to grow, and we have seen compliance rates for patients on drugs of around 90%; to date, more than 400 physicians have prescribed emphysema. And our focus remains on continued growth for the brands, including leveraging new data on differentiation. We expect the continued growth to come mainly from patients that might have decreased doses to manage safety while sacrificing efficacy with prednisone, as well as expanding into segments that might not be as engaged or have equal access to standard of care in the past. Another area of growth is the recently approved label expansion for emphysema. The promotional launch is going well, with the focus on updating payer policies and educating healthcare professionals on the benefit of early intervention. As noted last quarter, we have switched to a new specialty pharmacy in the U.S., and expects temporary operational inefficiencies to be resolved by the end of the third quarter.

Should be more than 400 physicians prescribing plaza.

In our focus will remain on the continued growth for the brands, including leveraging new data.

On differentiation.

We expect the continued growth will come mainly from patients that might have decreased those two managed safety, while sacrificing efficacy with PRASM zone.

As well as expanding into segments that might not be as engage our have equal access systemic risk and bath.

Another area of growth.

Is the recently approved label expansion part and Plaza.

The promotional launch is going well with the focus on updating payer policies and educating healthcare professionals on the benefit of our intervention.

As noted last quarter, we have switched to a new specialty pharmacy they last.

And expects temporary operational inefficiencies should be resolved by the end of the third quarter.

Now focusing on Translarna.

Marcio Souza: Now focusing on TransLearner, our XUS business remains very healthy, with organic growth of patients in all regions. We have entered the fifth year of TransLerna after its initial approval in Europe. At the time of their approval, we have established a study strive. Aiming to collect long-term effectiveness of TransLerna in non-sense mutation commercial patients treated in a real setting. We are delighted with the results coming out of STRIDE, including benefits in ambulatory and non-ambulatory patients. This data for more than 200 patients has now been presented at several congresses, demonstrating significant delays in loss of fumbulation and improved ventilatory function when compared to matched natural history controls. Additionally,

Our ex us business remains very healthy.

With organic growth of patients in all regions.

We have entered the fifth year of Translarna after initial approval in Europe .

At this time of that approval, we have established a study.

Strides.

Aiming chuckle lacks long term effectiveness of translarna in nonsense mutation commercial patients treated in our real Sadie.

We are delighted with the results coming out of stride.

Including benefits in ambulatory and non ambulatory patients.

This data far more than Q hundred patients.

We have now being presented at several Congress.

Demonstrating significant delays in loss of ambulation and improve vansittart function.

When compare to match natural any sort of controls.

Additionally.

Marcio Souza: We have received a significant order in the second quarter from the Brazilian government, following the approval of TransLerna by Amvisa. The number of patients identified in Latin America continues to grow, and we continue to work with payers worldwide to provide strontzyloma broadly to patients in need. Supporting the DMG community globally has been our very fabric for many years.

We have received a significant order in second quarter from the Brazilian government.

Following the approval of Translarna by on visa.

The number of patients identified in Latin America continued to grow.

And we continue to work with that Bayer's worldwide she'll provide surgeons on a broadly to patients he needs.

Supporting the DMD community globally has been our various happening for many years.

We have initiatives, our bold prescribers inpatient groups to advance the needs of DMD patients.

Marcio Souza: We have initiatives for both prescribers and patient groups to advance the needs of DMD patients. Our STRIVE Award for Patients and Patients Advocacy is in its fifth year, and we have received more than 30 qualified applications which will support better standards of care for patients globally. Moving on to TaxSetti and Waylivra.

Our strive award for patients and patient advocacy is in its 50 years.

And we have received more than 30 qualified applications, which is support bathers standard of care for patients globally.

Moving onto thanks, Secondly, deidre.

Marcio Souza: We have seen the first paid patient in Latin America for TaxSetti and the first prescriptions for Weylivra. We're excited about the potential of both products and our ability to leverage PTC's infrastructure and knowledge base. TxED is expected to be approved by INVISA in the coming months, which would trigger pricing and access negotiations with the government.

We have seen the floor space patient in Latin America for Tech Sadie.

And first prescriptions faraway deidre.

We're excited with the potential of both products and our ability to leverage ptcs infrastructure and knowledge base.

That said is expected to be approved by emphasizing the following months, which will trigger pricing and access negotiations with the government.

The patient care programs, including our nurse network supports is in place in all key countries to support a smooth launch.

Marcio Souza: The patient care programs, including our nurse network support, are in place in all key countries to support a smooth launch. Additionally, we are working closely with Axia to review the recent clinical results for Raylivra in familial partial lipodystrophy, or FPL, to determine the potential commercial strategy in Latin America. Now switching gears to gene therapy. As we approach the ADC Deficiency BLA submission later this year, the teams are busy finding patients and preparing the ground for a successful launch. In terms of patient identification, our global large-scale screening programs continue to roll out to all targeted regions and countries.

We are working closely with our CFO to review the recent clinical results for re lever up in familial partial lipodystrophy or SPL.

Sure that determine the potential commercial strategy in Latin America.

Now switching gears to gene therapy.

As we approach today due to the efficiency BLE submission later this year.

The teams are busy finding patients and preparing the ground for a successful launch.

In terms of patient identification, our global large scale with screening programs continue to roll outs to all targeted regions and countries.

For instance, we have recently agreed to partner with a key hospital in Germany to initiate a pilot's newborn screening projects.

Marcio Souza: For instance, we have recently agreed to partner with a key hospital in Germany to initiate a pilot newborn screening project using more than 90,000 newborn screens using the 3OMG method. It's an important initiative to realize our long-term vision to include ADC deficiency in newborn screening panels globally. In the U.S., the protocol-driven ADC deficiency screening in cryptogenic cerebral palsy will start screening patients this quarter, and non-protocol screening systems are in place globally. On the educational front, we're busy providing resources to physicians and caregivers to identify and provide the best care for ADC patients, including a series of webinars specifically targeting increasing diagnosis in AIDS. We have other requests, a specific ICD-10 code for ADC deficiency, which we expect to be accepted.

More than 90000 newborns screened using the trio MZ methods.

Jenny Boston's initiative to realize our long term vision two includes agency the efficiency in new blood screening panels globally.

In the last the protocol driven agency the efficiency screening in cryptogenic cerebral palsy.

We will start screening patients this quarter.

And the non protocol is screening systems are in place globally.

On the location of France, we're busy providing resource to physicians and caregivers to anyway to identify and provide best care for a dissipation.

Including a series of Webinars, specifically targeting increasing diagnose in agency.

We have also requests I specific IC did then called for a disease efficiency.

Which we expect to be accepted.

This will allow for better follow up of patients in the future.

Marcio Souza: This will allow for better follow-up of patients in the future. Moving on to some key clinical development updates. First, Sonata Lawrence.

Moving to some key clinical development updates first on the lawn.

We have finished enrolling is to study all 45, our dystrophin assessment study.

Marcio Souza: We have finished enrolling in Study 045, our Dystrophin Assessment Study, which, if positive, would support the resubmission of the TransLerna NDA in the United States for non-sense mutation DMZ. With the enrollment now complete, we expect the results in the first half of next year. As previously reported, we have requested a re-examination for the non-ambulatory label expansion in Europe, and our tentative date for an opinion is in October.

Which if positive would supports the resubmission of the Translarna NVCA in the United States for nonsense mutation DMD.

With the enrollment now complete we expect to results in the first half of next year.

As previously reported we have requested a reexamination for the non ambulatory label expansion in Europe .

And our tentative date for an opinion is in October .

And we are working diligently on the Resubmission just spots the documentation 40 rpms invasion.

Marcio Souza: And we are working diligently on the resubmission to support the documentation for the European Medicines Agency. For our ADC gene therapy, on top of the preparations for the PLA submission later this year, we have received approval for a pediatric investigation plan in Europe, which is a critical step towards the marketing authorization application submission. Our SA program readiness is evolving well, and we have selected Emory as the first site for the initial trial.

For our agency gene therapy.

On top of the preparations for the delay submission later this year.

We have received approval for our pediatric investigation plan in Europe .

Which is a critical step towards the markdown optimization application submission.

Our assay program redness is evolving well.

And we have selected Emery as the fore sight for the initial trial.

Since this is the first time, a gene therapy will be delivered to FH patients.

Marcio Souza: Since this is the first time a gene therapy will be delivered to a FA patient and to the cerebellum, it's key that we assess in this trial proper dosing and safety. But at the same time, we intend to assess both imaging and functional endpoints. Because it's an open-label study, we would expect to report on progress for the first few patients in late 2020. These are exciting times for PTC as we continue to deliver on our therapies to support rare disease patients. I'll now hand the call over to our Chief Financial Officer, Emily Hill. Emily?

And to the cerebellum.

It's key that we assess in this trial proper dosing and safety.

But at the same time, we intend to assess both imaging and functional endpoints.

Because it is an open label study.

We would expect to report on progress for the first few patients in late planted 20.

This is an exciting time for PTC as we continue to deliver on our therapies just supports the rare disease patients.

Ill now hand, the call over to our Chief Financial Officer, Emily Hill Emily.

Thanks, Mike now I'm happy to be joining the call today for the first time in the CFO capacity.

Emily Luisa Hill: Thanks, Marcio. I'm happy to be joining the call today for the first time in the CFO capacity. It's been a great experience to be part of PTC's growth in the last five years as we've developed from an R&D stage company to a global commercial company still driving innovative R&D. I'm eager to continue to be an integral part of our next growth phase as we anticipate submissions, approvals, and subsequent launch of our first gene therapy products and the advancement of several R&D programs. As you know, our second quarter press release was issued a short while ago that summarizes the details of our financial results for the second quarter of 2019. Please see that release for further details.

In a great experience to be part of Ptcs growth in the last five years since we've developed from an R&D stage company to a global commercial companies still driving innovative R&D.

Im eager to continue to be an integral part of our next growth phase and we anticipate submissions approvals and subsequent launch of our first gene therapy product and the advancement of several R&D program.

As you know our second quarter press releases issued a short while ago like summarizes the details of our financial results for the second quarter of 2019.

Please see that release for further details.

Emily Luisa Hill: I'll start with a few comments on our financial performance in the quarter and then reiterate our guidance for the full year 2019. Starting with our top-line results, we reported $85.4 million in combined net revenue across our commercial portfolio in the second quarter of 2019, compared to combined revenue of $68.1 million for the second quarter of 2018. TransLarna Net Product revenues were $57.8 million for the quarter. This compares to $47.8 million in the second quarter of 2008. This growth includes the expansion of TransLarnaxUS, including regulatory approval and an annual contract with Brazil. For IMSLASA, we reported net product revenues of approximately $27.6 million for the second quarter of 2019, which compares to $20.3 million reported in the second quarter of 2018. We are working towards establishing EMPLASA as the standard of care for all patients in the U.S. and are happy to be able to bring EMPLASA now to patients as young as two years of age.

I'll start with a few comments on our financial performance in the quarter and then reiterate our guidance for the full year 2019.

Starting with our top line results, we reported $85.4 million and combine that revenue across our commercial portfolio in the second quarter of 2019 compared.

Two combined revenue and $68.1 million for the second quarter of 2018.

Translarna net product revenues for 57.8 million for the quarter this compared to $47.8 million in the second quarter 2018.

This growth includes the expansion of Translarna ex us, including regulatory approval, an annual contract with Brazil.

Foreign flagged that we reported net product revenues of approximately 27.6 million for the second quarter of 2019, which compared to 20.3 million recorded in the second quarter of 2018.

We are working towards establishing himself as the standard of care for all patients in the U.S.

And are happy to be able to bring in plaza now to patients as young as two years of age.

Operator: Continued growth of the DMD franchise and a contract with Brazil for TransLarna gives us confidence to reiterate our 2019 DMD franchise revenue guidance of $285 to $305 million. We have also outlined the opportunity for our pipeline to generate potential combined revenue in excess of $1.5 billion by 2023. Non-GAAP R&D expenses were $54.5 million for the second quarter of 2019, excluding $5.5 million in non-cash stock-based compensation expense, compared to $28.7 million for the second quarter of 2018, excluding $3.9 million in non-cash stock-based compensation expense. The increase in R&D expense reflects our strategic investment in advancing the gene therapy platforms, splicing programs, and other research programs, as well as the advancement Non-GAAP SG&A expenses were $43.8 million for the second quarter of 2019, excluding $5.4 million in non-cash, stock-based compensation expense, compared to $29.4 million in the second quarter of 2018, excluding $4.1 million in non-cash, stock-based compensation expense, reflecting continued investment to support our commercial activities, including expanding our commercial portfolio.

Continued growth of the DMD franchise, and a contract with Brookdale for Translarna gives us confidence to reiterate our 2019 DMD franchise revenue guidance to $85 million to $305 million.

We've also outlined the opportunity for our pipeline to generate potential combined revenue in excess of 1.5 billion by 2023.

non-GAAP R&D expenses were $54.5 million for the second quarter 2019, excluding 5.5 million and non cash stock based compensation expense compared to 28.7 million for the second quarter 2018, excluding 3.9 million and non cash stock based compensation expense.

The increase in R&D expense reflects our strategic investment in advancing the gene therapy platform, placing program and other research programs as well as the advancement of preclinical pipeline.

non-GAAP SDMA expenses were 43.8 million for the second quarter 2019, excluding 5.4 million and non cash stock based compensation expense.

Compared to $29.4 million in the second quarter of 2018, excluding 4.1 million and non cash stock based compensation expense.

Reflecting continued investments to support our commercial activities, including expanding our catalog Marshall portfolio.

I would also like to reiterate our non-GAAP R&D and ask DNA expense guidance for full year 2019, $360 million to $370 million, excluding non cash stock based compensation expense of approximately $35 million.

Operator: I would also like to reiterate our non-GAAP R&D and SG&A expense guidance for full year 2019 of $360 to $370 million, excluding non-cash, stock-based compensation expense of approximately $35 million. The net loss for the second quarter of 2019 was $41.8 million compared to a net loss of $9.5 million for the second quarter of 2008. Cash, cash equivalents, and marketable securities totaled approximately $363 million at June 30, 2019, compared to approximately $227 million at December 31, 2018. We are proud to have built a global biotech company that is in a financial position to continue to execute on our long-term strategy. I'll now hand the call over to the operator to start our question and answer session.

Net loss for the second quarter of 2019 was $41.8 million compared to a net loss of $9.5 million for the second quarter of 2018.

Cash cash equivalents and marketable securities totaled approximately $363 million at June Thirtyth 2019, compared to approximately 227 million at December 30, Onest 2018.

We are proud to have built a global biotech company that is in a financial position to continue to execute on our long term strategy.

I'll now hand, the call over to the operator to start our question and answer session.

Operator.

Thank you ladies and gentlemen, if you have a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.

Operator: Thank you. Ladies and gentlemen, if you have a question at this time, please press star then one on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from the line, Roger Versailles, from William Blair. Your line is open. Thanks for taking the time to answer the question.

To prevent any background noise, we ask that you. Please place your line on mute. Once your question has been stated.

Our first question comes from the line.

Roger for SAP of William Blair.

Your line is open.

Thanks for taking the question.

Just a quick question on revenue guidance for 2019 I think.

Unknown Attendee: Just a quick question on...

Unknown Attendee: Revenue Guidance for 2019. I think you guys did $140 million this year. I'm just trying to figure out, you know, with the naval expansion and Brazil, what are you kind of expecting to get to the midpoint there from those new growth drivers? Thanks.

You guys did 140 million this year.

I'm, just trying to figure out what the label expansion.

And Brazil.

What do you kind of expecting to to get to the midpoint there from from those new growth drivers. Thanks.

Oh, thanks for costs.

Emily.

Emily Luisa Hill: Thanks for the call. Emily?

Yes, thanks for the color as you know we are happy to be reiterating our revenue guidance for 2019 of $285 million to $305 million for DMD franchise that reflects.

Emily Luisa Hill: Thanks for the call, Raju. We are happy to be reiterating our revenue guidance for 2019 of $285 to $305 million for our DMD franchise. That reflects the anticipated Brazil order for current patients' underlying demand. It does not contemplate the expansion of two- to five-year-olds in the emplaza label, as that is a solar process.

The anticipated bridge order for current patients underlying demand does not contemplate expansion as two to five year olds in the inside the label as that as a follow up.

Great and just one on kind of your small molecule platform.

Can you just talk a little bit about some of the learnings that you had with Reza plan.

Unknown Executive: Great. And just one on kind of your small molecule platform, you know, can you just talk a little bit about some of the learnings that you have had with RISDAPlan and the prior small molecule splicer that you're going to take forward?

On the prior four molecule splice or that you're going to take forward.

Sure, Yes, so for the in the rest of the plan.

Obviously, we've been doing this for some time and I think we've learned in terms of thinking about mechanism of action and how to focus on that and over the years, we've built quite a proprietary library of small molecules everything have.

Unknown Executive: Sure, yeah, so for the risk deployment, you know, obviously, we've been doing this for some time, and I think we've learned in terms of thinking about the mechanism of action and how to focus on that, and over the years, we've built quite a proprietary library of small molecules that we think have, you know, that give us a unique advantage in being able to target splicing. And also, we've learned a bit about, in terms of the site, the first site that we're hitting, especially in the plant, is a U1 binding site that has mismatches there. Now, as you probably remember from some of our calls, most of the time it's a perfect interaction between the U1 and the 5' splice site, but in SMN it's not, and that's why it's leakier, and our molecule, in a sense, increases the interaction to allow splicing efficiency to occur.

That give us.

Our unique advantage in being able to target splicing and then also we have learned a bit about in terms of of the of the site. The first site that we're hitting specially like group a plant in the year. One binding site that has altered that have mismatches there now.

As you probably remember maybe from some of our call most of the time, it's a perfect interaction between the year, one and five prime slice side, but.

In Esa man, it's not and Thats why its leak year and our molecule in a sense increases the interaction to allow displacing efficiency to occur and we've learned a lot about that interaction that allows us in the sense.

To do it through a.

Our high throughput three that lift for than more to other targets as well and as a consequence of that we've been able to move quite rapidly for familial disorder know me a good example for a lot of times. When you did it once you ask yourself can you do it multiple times and this is again, a clear example of getting ft to effect and a second molecule that specific from for that particular mutation and then we have grown on the do it on a third time touring late stage chemical optimization for Huntington disease. So from a big picture perspective, I think you can see that what you'd like to be able to do is use a platform to be able to get multiple compounds out of that you see that we are we able to use our our knowledge there understanding the mechanism of action to actually move into multiple other targets and move them quickly through the discovery process into the into the.

Unknown Executive: So a lot of times when you do it once, you ask yourself, can you do it multiple times, and this is, again, a clear example of getting FD to a second molecule that's specific for that particular mutation. And then we've gone on to do it a third time, and it's where we are in late stage chemical optimization for Huntington's disease. So from a big picture perspective, I think you can see that what you'd like to be able to do is use a platform to be able to get multiple compounds out of that, and you see that we're able to use our knowledge, the understanding, and mechanism of action to actually move into multiple other targets and move them quickly through the discovery process into the plant.

Operator: Great, thanks. Thank you. Our next question comes from Alethea Young of Canner Fitzgerald. Your question, please.

Clinical development.

Great. Thanks.

Thank you. Our next question comes from Ali if you're young of Cantor Fitzgerald. Your question. Please.

Hey, guys. Thanks for taking my question and congrats on the quarter two questions for you can you talk a little bit more about AIDC deficiency and kind of what's going on with the manufacturing there and the progress toward getting an approval and then I was just curious if you guys might give an update on how many patients you ballot AIDC deficiency I think the last time, we got an update was on January thanks.

Operator: Hey guys, thanks for taking my question and congrats on the quarter. I have two questions for you.

Unknown Attendee: Can you talk a little bit more about AADC deficiency and kind of, you know, what's going on with the manufacturing there and the progress toward getting an approval? And then I was just curious if you guys might give an update on how many patients you found with AADC deficiency. I think the last time we got an update was in January. Thanks.

Yes, hi, Olivia thanks for the other questions that we're we're actually really quite excited about.

Marcio Souza: Yeah, hey, Alicia, thanks for the question. Jeff, we're actually really quite excited about moving to AADC deficiency. As we've said, all things are on track for submitting the BLA this year for potential approval next year. And obviously, as you know, the key thing is getting manufacturing completed and done. And Marcy, do you want to talk a little bit about that?

Moving ABCD deficiency as we've said all things are on track for submitting the ability this year for a potential approval next year and obviously as you know the key thing is on getting manufacturing are completed and done and Murphy want to talk a little bit about that sure sure absolutely hail. It yes. So a couple of steps here rights towards the submission of the BLA and hopefully the approval next year. Our subsequent to that so the manufacturing group continue to work very hard on all the steps that we agreed with the FDA.

Marcio Souza: Sure, sure, absolutely, Haley. So, a couple of steps here, right, towards the submission of the BLA and, hopefully, approval next year as a consequence of that. So, the manufacturing group continues to work very hard on all the steps that we agreed with the FDA towards all the bets that have to be made before the submission, and obviously the comparabilities on those, making sure all the analytical methods are validated in accordance with the discussions we had with the agency, and then all the other parts of the BLA. We do expect to soon be meeting with the FDA in relation to the pre-submission for the NDA itself, It's normally taken on things like that, where it's more structurally and administratively how the submission is going to be going, but from all the aspects in general, it's all finalization of documents right now, other than on the manufacturing where we're still working towards the release of the commercial batch based on the agreements we have with the agency.

Towards the.

All the batch that have to be made to be part of the submission obviously the compare billets on those making sure all the analytical methods is validated in accordance to the discussions we had with the agency and then all the other parts of the BLE. We do expect to soon be meeting with the FDA in relation to the pre submission for DMD eight south which is a procedure staff. It's normally taken on things like that where it's more structurally and administrative Lee how the submission is going to be going but.

From all the aspects in general we'd solve finalization of documents right now other than on the manufacturing that are we still working towards the release of the commercial batch based on the agreements we have with the agency.

But since our last update that is nothing really major already been minor to that extends to happen that is not in the plan like our it's all sequential at this point in time I want to make sure we not only manufacture to the specs that we agree with the agency, but also have enough inventory.

Marcio Souza: But since our last updates, there is nothing really major or even minor to that extent that has happened that is not in the plan, like it's all sequential at this point in time. I want to make sure we not only manufacture to the specifications that we agree with the agency but also have enough inventory for the time of launch, and the technical operations group is working really hard on that, together with and under the supervision of our QALYS team, because we know how important it is to make sure our processes are not only efficient but compliant as well. In terms of the patient finding initiative, as I mentioned in my prepared remarks, there's a number of things we're doing. One of them is what we call non-protocol screening, and that's basically giving physicians the ability globally to screen at-risk or other patients that they might have misdiagnosed before with the DDC gene or the 3-OMD methods in the blood.

For the time of launch and the technical operations group is working really hard with that together.

With an under the supervision of our quality.

Team because we know how important it is to make sure our profits are not only efficient but compliance as well.

In in terms of the outpatient finding initiatives.

As I mentioned on the.

Our prepared remarks, there is a number of things we are doing.

One of them is the no what we call non protocols screening and Thats basically, giving physicians the ability globally to screen the at risk or other patients that they might have mis diagnosed before with the DDC gene are the three AOMT amat tools into bloods.

Marcio Souza: This is going very well, and we've been identifying patients pretty much every week and progressing, and we're going to give an update in the future on the exact numbers. The second process, which we believe will actually yield more patients in the identification phase, is protocol-driven, and that has to go through the IRB approval, the contracting phase, and up until a few weeks ago, this being a little bit slow in the sense that you have to go through all the steps and make sure they're all accomplished. We're now in the process of restarting that, and we expect to have the first patients screened in September. So our expectation is that later in the year, we'll be able to provide an update on the exact numbers.

This is going very well and we being identifying patients like pretty much every week.

And progressing and im going to give an update in the future on the exact numbers.

The second process, which we believe to actually enrolled more patients on Densification is the protocol driven and that has to go through the IR be approvals the contracting phase and up to a few weeks ago. This being a little bit slow in a sense that you have to go for that all that steps to make sure that all accomplished are now at the process to start that and we expect to have the first patients are screened in September so.

Our expectations are later in the year, we'll be able to provide an update on the exact numbers and I think.

The work is it's been exciting and gratifying and with that.

Just to remind you weve found there is over 80 different to Leo that we've identified which really gets by the notion when people thought there was the founders effect. So we get more and more convinced everyday on the number that we had told you previously about 5000 patients commercially so that are commercially viable. So we're excited to keep moving this forward were excited that the our process. Thus far in the manufacturing is moving along and we anticipate the submission with the completion of the manufacturing of this year.

Unknown Executive: I think the work has been exciting and gratifying in that, just to remind you, we've found there are over 80 different alleles that we've identified, which really gets by the notion that there was the founder's effect. So we get more and more convinced every day about the number that we had told you previously, about 5,000 patients commercially that are commercially viable. So we're excited to keep moving this forward; we're excited that the process thus far in the manufacturing is moving along, and we anticipate submission with the completion of the manufacturing this year.

Great. Thank you.

Thank you.

Thank you. Our next question comes from Brian Abrahams of RBC capital markets. Your line is open.

Hi, This is Bert on for Brian and Thank you guys for taking a question.

Hi couple in the region should tax year program can you talk about any preclinical maybe functional data that you have to complement the protection expression data you've shown in the poor sign in non human primate models that gives you confidence that the level of expression you are able to achieve with the gene therapy will translate to functional improvements and then also related to that will you be building will.

Operator: Great, thank you.

Operator: Thank you.

Operator: Thank you. The next question comes from Brian Abrahams of RBC Capital Markets. Your line is open. Hi, this is Bert on behalf of Brian. And thank you guys for taking our questions. I had a couple on the Friedrich's ataxia program. Can you talk about any preclinical, maybe functional data that you have to complement the protaxin expression data you've shown in the porcine and non-human primate models that gives you confidence that the level of expression you're able to achieve with the gene therapy will translate to functional improvements? And then also, related to that, will you be

The process of building out your own gene therapy manufacturing capabilities.

To produce material for clinical study be rate limiting for being able to start the clinical trial.

In Epay patient.

Sure maybe let me start and then I can pass or not but I suppose the upgrade program as you alluded to just to remind everyone else on the call we were able to and.

Obviously inject into the cerebellum and be able to get a substantial production offer taxing their to the levels that we would think.

Unknown Attendee: Will you be building, will the process of building out your own gene therapy manufacturing capability...

Would be.

Obviously to levels that we think would obviously change the course of the disease. So we were happy with the level there aren't any great model in the sense that we have that we'll be able to.

Unknown Executive: To produce material for a clinical study be rate limiting for being able to start the clinical trial in

Be able to do the functional comparisons, but we feel pretty confident that.

Unknown Executive: Sure. Maybe I can start and then I can pass it on.

That were being able to bring it to the right place and that.

Unknown Executive: So the F.A. program, as you alluded to, just to remind everyone else on the call, we were able to obviously inject into the cerebellum and be able to get substantial production of frataxin there to the levels that we would think would be, obviously, to levels that we think would obviously change the course of the disease. So we were happy with the levels. There aren't any great models in the sense that we have that would be able to do the functional comparisons, but we feel pretty confident that we'll be able to bring it to the right place and that, in our discussions with all of the key opinion leaders, we would anticipate that it would have effects as a consequence of that. In terms of manufacturing, we're on target in terms of manufacturing, getting ready to get manufactured for the IND. That's ongoing now. Obviously, as I think we mentioned, we have a site that we'll be leasing, but this is being done initially at a different facility that we may ultimately come back to later as the facility opens to produce it there.

In our discussions with all of the key opinion leaders would anticipate that would have affected as a consequence of that in terms of the manufacturing. We're on target in terms of our manufacturing getting ready to get manufacturer for the high empty. If thats ongoing now we're not obviously as I think we mentioned we have are a site that we're we'll be leasing of this is being done initially at a different facility that were may ultimately come back later at the facility open to produce it there.

Great. Thank you.

Thank you. Our next question comes from the line of Gena Wang of Barclays. Your question. Please.

Hi.

This is Peter for Gena Wang Thanks for taking my question.

So I guess, maybe two quick couple of months for me.

Protect study how should we think about.

I guess reimbursement decision process post approval and how would the pricing.

Operator: Great, thank you. Thank you.

Look like relative to the U.S. and I guess through belatedly, how should we think about revenue contributions from distribution for the first few quarters.

Operator: Our next question comes from the line of Gina Wang of Barclays. Your question, please. Hi, this is Peter Fujino-Ng. Thanks for taking our question. Um, so I guess maybe two quick couple ones for me. For tech study, how should we think about, I guess, the reimbursement decision process post approval and how would the pricing look relative to the U.S., and I guess relatedly, how should we think about revenue contributions for this region in the first, you know, first few quarters?

In Britain first yes. So thanks, so much Peter for for the questions. So first of all on Tech savvy and water, we expect softer DEA approval, which is upcoming from visa.

Obviously that is to process rights as we've described before one is the individual patients reclass that would have called named patient sales and that should continue to be.

Requested by the patients and approved individually and you might have seen that together first patients in the region reimburse, which we feel.

Marcio Souza: So, thank you so much, Peter, for the questions. So, first, on TxEDI and what we expect after the approval, which is pending from NVISA. Obviously, there are two processes, right, that we described before.

Really proud off.

And that's going to probably be anywhere between the us price in European price based on the negotiations with the government now we have submitted as far as is requested now by the regulation there up price should be commercializing the country. We fully expect that that's going to be some negotiation. Once it's approved and then that is a cap. What is it's called at is the discounts that is applied on top of that of around 20%.

Marcio Souza: One is the individual patient's request, what we call named patient sales, and that should continue to be requested by the patients and approved individually. And you might have seen that we got the first patients in the region reimbursed, which we feel really proud of. And that's going to probably be anywhere between the U.S. price and the European price, based on the negotiations with the government. Now, we have submitted, as is requested now by the regulation there, a price to be commercialized in the country. We fully expect that there's going to be some negotiation once it's approved, and then there is a cap, what it's called, and it's a discount that is applied on top of that of around 20%. So it's going to be a reduction on the overall price that is normally anchored to the United States FSS price. So there is some reduction that is going to be accounted for. We fully accounted for that in our internal projections on the model and the guidance for 2023 that we gave of $150 million for the product.

So it's going to be a reduction on the overall price that is normally anchored should the United States FSS price. So that is some reduction that it's going to be accounted for we fully accounted for that in our internal projections on the model in the guidance for 2023 that we gave of $150 million for the products.

Our it integration our patients and aligning KNOP is being quite positive. So we see the the launch delay late this year and next year to be while.

Patient by patient in this first phase to be quite productive and positive for PTC.

In terms of the contribution.

Of the region for for the overall mix of the company as Emily mentioned.

We did receive a large order for translarna, which were extremely proud off because it means that patients can have continuity affect SaaS and it's for the entire year. So we know that as it becomes a little bit more irregular.

Marcio Souza: Identification of patients and the lining up is quite positive, so we see the launch late this year and next year to be patient by patient in this first phase to be quite productive and positive for PTC. In terms of the contribution of the region to the overall mix of the company, as Emily mentioned, we did receive a large order for TransLerna, which we're extremely proud of because it means that patients can have continuity of access, and it's for the entire year. So we know that it becomes a little bit more irregular, although still fairly lumpy in terms of the size of the orders, less irregular in terms of patients receiving it. It's an important region for us, but it's not the biggest region in the world for TransLerna. So, again, trying to balance the general demands globally while giving the emphasis there of all patients being on drugs.

Although still fairly lumpy in terms of the size of the orders last irregular in terms of patients receiving as it is an important region for us.

But it's not the biggest region in the award for Translarna. So again trying to balance the general demands globally, while giving the Ams is that all patients being on drugs.

Great. Thank you sorry.

A quick follow up if I may 1st when should we expect any updates from makeup part one and part two of higher commissions on fish. Thank you very much.

Yeah. So.

The update of political will be doing that at subsequent meetings for for part one and part one of each of fire efficient SUNFISH at the world muscle WMS, maybe that will be will be presenting the continuation of that for part one.

Part two will be.

Marcio Souza: Thank you very much.

Unknown Executive: So, we'll be doing that at subsequent meetings for Part 1 of each of FireFish and Sunfish at the WorldMuscle WMS meeting that we'll be presenting the continuation of that for Part 1. Part two will be sometime next year.

Next year some time.

Great. Thank you very much.

Some questions. Thank you.

Thank you. Our next question comes from Martin Northstar of Credit Suisse. Your line is open.

Hey, Thanks for taking my question most of them have been.

Maybe just.

To follow up on on that theme. There is there any plan to present or kind of publicity the preclinical data from the Huntington's Spicing program.

Operator: Great, thank you very much for that. Thank you. Thank you. Our next question comes from Martin Oster of Credit Suisse. Your line is open.

Operator: Hey, thanks for taking the question. Most of them have been asked, maybe just to follow up on that last theme there. Is there any plan to present or kind of publish any of them?

In the balance of this year or ahead of the R&D next year. Thanks.

Yes, thanks, so riveting.

Moving forward on the Huntington's program, we anticipate.

And a clinical candidate this year with it going into the clinic next year, we're always careful in terms of timing of when we publish.

Unknown Attendee: Preclinical Data from the Huntington's Splicing Program by the balance of this year or ahead of the IND next year. Thanks. Yeah, thanks. We've been moving forward on the Huntington's program; we anticipate a clinical candidate this year, with it going into the clinic next year. We're always careful in terms of timing of when we publish the, you know, the work on Huntington because it's a structure and we take our time in terms of putting out the structures. So the publication of those is undefined as such. But we'll probably be talking further on at science day or analyst day about what the Huntington so that you get more information and more details about what we're doing.

The.

The work on Huntington because of the structure and we.

We take our time in terms of putting out the structures. So the publications of those are undefined as of of that but we'll probably be talking either science day are.

Analyst day about further on about what what the.

About Huntington for that to get more information in more detail about what we're doing.

Are you contemplating an analyst day later 19 or sometime next year.

Sometime next year.

Okay, great. Thank you.

Thank you. Our next question comes from Vincent Chen Bernstein.

Your line is open.

Congrats on progress and thanks for taking the question another follow up on hunting done them.

Unknown Executive: Are you contemplating an animal stay later in 19 or sometime next year?

I was wondering if you could provide a little bit more detail and color on the status of the preclinical Huntington's program and what's left to be done before you can get into the clinic I guess I'm a little bit more on where specifically are you in that lead optimization process. What are properties, you're focused on and I guess up maybe pointedly.

Unknown Attendee: So come next year.

Operator: Okay, great. Thank you. Thank you. Our next question comes from Vincent Chen of Bern State. Your line is open.

Operator: Congratulations on your progress and thanks for taking the question. Another follow-up on hunting guns.

Unknown Attendee: I was wondering if you could provide a little bit more detail and color on the status of the preclinical Huntington's program and what's left to be done before you can get into the clinic. I guess a little bit more on where you are in the lead optimization process, what properties you're focused on, and, maybe, more specifically. Are you at a point where you have compound clusters or compounds that appear adequately specific for the targeted pseudo-exon, or is there more to be done on the specificity front and reducing the risk of off-target effects?

Are you at a point, where you have compound clusters are compounds up you're adequately specific for the target pseudo Exxon or is there more to be done on the specificity frontend.

Reducing risk off target effects.

Yes, yes, thanks for the question it.

There's a lot of chemistry thats been ongoing we're in the.

Relatively late stages that we anticipate an uptick in of a clinical candidate now a lot of it is moving through the screening process. The safety toxicology studies that we do and that just takes some time. So we have a set of of scale.

A small set of compounds from a from a scaffold that we've identified form of capital that we've identified that we like that we anticipate where the clinical candidate will come from and is just now going through of the myriad of of assets that are required. When you think about sort of what I always call. The underbelly of what you've got to do for given the small molecule through.

Unknown Executive: Yeah, thanks for the question. There's a lot of chemistry that's been going on. We're in the relatively late stages if we anticipate picking a clinical candidate. Now a lot of it is moving it through the screening process, the safety toxicology studies that we do, and that just takes some time. So a lot of testing to make sure, or having an understanding of the chemical properties and then our own internal safety toxicology that allows us to define what the threshold and window are.

On R&D process, there's a slow a lot of testing to make sure or have an understanding of the.

Oh, the chemical properties and then the our own internal third to talk safety toxicology that allow us to define what the threshold and window. Our merger, yes of course, and Vincent just to add a little bit to everything they store just SaaS right. So specific properties that we're looking this compound. So obviously our distribution in that in that all the structures of the CNS is important for us we see that as a sharp coming off the other approach to really having the reduction of the hunting 10, and specifically on the dip structures. So thats far as important but at the same time that is a lot of residual disease. After ferric lease or wants to make sure that is a distribution very methodically as well so being an oral molecule or molecules as analytics by the minutes, that's quite important as Stuart mentioned that we have a number of viable scaffolds that we've been working on from Dan at this.

Marcio Souza: Yeah, yeah, of course, and Vincent, just to add a little bit to everything that Stuart just said, right, so specific properties that we are looking at in these compounds, obviously, distribution in all the structures of the CNS is important for us. We see that as a shortcoming of the other approach to really having the reduction of the Huntington and specifically the DIP structures. So that's important, but at the same time, there is a lot of residual disease peripherally, so we want to make sure there is a distribution peripherally as well. So being a neural molecule or molecules, as I'm going to explain in a minute, that's quite important. Stuart mentioned that we have a number of viable scaffolds that we've been working on.

Marcio Souza: From then on, at this point in time, while it's still early, since we're going to be going to GOP talks hopefully soon, we have multiple viable candidates, and we intend to continue with them all the way potentially to the clinic since safety margins and even the ability of them to penetrate different tissues or to have different properties on the spectrum of the disease since we know that Huntington is not necessarily just one manifestation, but that it's like different types of patients that So, a very extensive approach. We have a really dedicated and large number of people working on this. Expect to declare one or more candidates this year and be in the clinic next year.

This pointing time why would skew or lease since we're going to be going to GLP tox hopefully as soon.

We have multiple viable candidates and we intend to continue with Dan.

Other way potentially to the clinic.

Since safety margins and even the ability of them to penetrate different tissues are to have.

Different properties on the spectrum of the disease. Since we know the Huntington is not necessarily just one manifestation, but that is like different types of patients semis.

Benefits from different profiles. So very extensive approach we have like really dedicated and large number of people working on this expect to declare one or more I can state this year and beyond Atlantic next year.

Operator: Thank you. Thank you. Our next question comes from Joel Beatty of Citi. Your question, please.

All right. Thank you.

Thank you. Thank you.

Thank you. Our next question comes from Joel Beatty of Citi. Your question. Please.

Operator: Hi guys, this is Sean Egan calling in for Joel. Thank you for answering my questions. I have three today. The first one is, on the heels of today's positive, Day 3, WayLeaver, Day Day, and FPL, can you try to frame any early work you've done on the Latin Am opportunity there, and do you anticipate that it will alter your WayLeaver sales for us in any way?

Hi, guys. This is Sean Egan, calling in for Joel. Thank you for taking my question.

Three today.

First one is on the heels of today's positive phase three where LIBOR today yeah.

Just trying to frame any early work you've done on the Latin and opportunity there and it has a bit of Walter you're ready for sale for us anyway.

Marshall yet not thanks on that now Thats, a great question and we're Super proud of the work Ioannis and Akcea has done here to help does come in at CN and with the results.

Marcio Souza: Marcio? Yeah, thanks for that. No, that's a great question, and we're super proud of the work Ionis and Axia have done here to help this community, and with the results that they're sharing today, and we shared as well. The opportunity basically doubles for us in Latin America when we add both FCS and SPL together. It's a perfect overlap.

That they sharing today and we shared as well.

The options basically doubles for us in Latin America, when we adds both FCS and FPL together, it's a perfect overlap is the same physicians diagnosing this our screening and monitoring programs already contemplating one of the reasons and we alluded to that before but maybe not so explicitly that we did not submit.

Marcio Souza: It's the same physicians diagnosing this. Our screening and monitoring programs are already contemplating this. One of the reasons, and we alluded to that before, but maybe not so explicitly, that we did not submit to UNVISA or other regulatory agencies because we're waiting for the readout of this trial to submit a broader label with a bigger indication, which we intend to do. We're going to be reviewing, and we'll review the results, preliminary results with the Axia team before today's disclosure. We share their view and enthusiasm in relation to that, and we're going to review the full results soon, as soon as they are available, and then file for approval in Latin America. I think what you can say right now is that patient identification was always on our radar screen. We're going to continue to look into them. We have a number of cases already that have been reported to us, and you're going to definitely drive to get these patients the treatment they deserve.

Two of these are all the regulatory agents because we're waiting for the results of this trial to submit a broader label with a bigger indication, which we intend to do we're going to be revealing we reviewed the the results preliminary results. Our thought was the akcea team before todays disclosure, we share their view and enthusiasm in relation to that and we're going to review the full results soon as soon as it is available and then file for part a submission in Latin America I think what you can say right now is that patient identification was always in our hearts.

Screen, we're going to continue to look into it then we have a number of cases already.

They are being reported to us and youre going to definitely drive to get this patients that treatment they desired.

And actually maybe from a point of view the.

Just based on what we've talked about before in terms of the vision and the 2023. The numbers that we gave previously did include appeal as BARDA, yes, a part of that for that.

Something the upside as well.

Great Yeah completely makes sense remarks, you know you mentioned on initial newborn screening efforts in Germany have you had any initial discussions with the Secretary Advisory Committee around getting 80, a deficiency and other national rough.

Unknown Executive: The connection may be from a point of view, just based on what we talked about before, in terms of the vision for 2023, but the numbers that we gave previously didn't include FPL as part of it.

Unknown Executive: A part of that, so that's something on the upside as well.

Yes, so more generic discussions to be honest, Sean at this point in time, because the matters that we are validating.

Marcio Souza: For Marcio, you mentioned initial newborn screening efforts in Germany. Have you had any initial discussions with the Secretary's Advisory Committee around getting a D.C. deficiency out of the National Arrest?

Now internationally it like using the blood sample and being widely available has not been tested for RMBS, yes. So one of the key things we're trying to do with this large hospitals in Germany is to not only screen. This babies and provides a potentially like like saving diagnosis and treatment for them, but also to make sure that this past work at scale. So we can bring to other places like the United States saw this conversations are ongoing and as I mentioned again on the remarks, it's part of a broader strategy to make sure that the time of launch our shortly thereafter, we have an available platform for newborn screening that can be readily to deploy.

Marcio Souza: Yeah, so more generic discussions, to be honest, Sean, at this point in time, because the methods that we are validating now internationally, like using the blood sample and being widely available, have not been tested for MBS yet. So one of the key things we're trying to do with this large hospital in Germany is to not only screen these babies and provide a potentially life-saving diagnosis and treatment for them, but also to make sure that these tests work at scale so we can bring them to other places like the United States. So all these conversations are ongoing, and as I mentioned in my remarks, it's part of a broader strategy to make sure that at the time of launch or shortly thereafter, we have an available platform for newborn screening that can be readily deployed.

Great and my last question is can you provide any update on the enrollment or the Presymptomatic Rainbow fish study and southern Europe when were evaluating as David said is the more important to kind of show comparability to spinraza nickel, Jonathan or other points of differentiation that are important to consider.

So I think we'll we'll probably be giving an update on Ray will force next year.

From the comparability I think obviously the pace X symptomatic patient one would anticipate maybe having.

Marcio Souza: And my last question is, can you provide any update on the enrollment for the pre-symptomatic rainbow fish study? And kind of when you're, when we're evaluating this data set, is it more important to kind of show comparability to Cynorhiza and Zolgensma, or are there points of differentiation that they're important to consider?

Improvements in that's been seen within the data we've expect.

Results like that as well that the patients will ultimately improve obviously, we think that the advantage of being able to pass not only get to the blood brain barrier, but get into all of the tissues as well.

It moves ban is not only early but also as the.

The babies and mature and their Brooklyn barrier is no longer is open that they'll still get the benefit of a.

Unknown Executive: So, I think, you know, we'll probably be giving an update on Rainbow Fish next year. From the comparability, I think, obviously, the asymptomatic patient, one would anticipate maybe having, you know, improvements, and that's been seen within the data. We'd expect results like that as well, that the patients would ultimately improve. Obviously, we think that the advantage of being able to pass, not only get to the blood-brain barrier but get into all of the tissues is an advantage, not only early, but also as the babies mature and their blood-brain barrier is no longer as open, so they'll still get the benefits of a molecule that can both go to the CNS as well as distribute into other tissues.

Of of of of a molecule that can both go with CMS as well have to distribute into other tissues.

Great. Thank you for your interest thank you.

Thank you. Our next question comes from Eric Joseph J.P. Morgan Your line is open.

Hey, guys. Thanks for taking the questions.

Maybe just.

Biology question for the Huntington gross price expressing program.

So understanding the mechanism likely be promoting both the turnover of the new and the wealth.

I think in protein so.

So im just wondering if you could speak a little bit the native function of Huntington and sort of how from a biological perspective, how wide of a therapeutic window youd anticipate with his approach and preclinical you are you able to.

Analyze a relative turnover of the mutant versus the wild type curves and the pricing and I guess, if there are any different safety considerations.

Operator: Great, thank you for your answers.

Operator: Thank you. Thank you. Our next question comes from Eric Joseph of J.P. Morgan. Your line is open. Hey guys, thanks for taking the questions.

We're meaningfully different safety considerations with this obligation versus the.

The other.

Approaches that are directly administered to the CMS. Thanks.

Eric William Joseph: Biology question for the Huntington's oral splicing program. If you're understanding the mechanism correctly, you'd be promoting both the turnover of the mutant and the wild-type Huntington protein. So I'm just wondering if you could speak a little bit about the native function of Huntington and sort of how, from a biological perspective, how wide of a therapeutic window you'd anticipate with this approach. And preclinically, are you able to, you know, analyze the relative turnover of the mutant versus the wild-type version of the protein? And I guess if there are any, you know, different safety considerations or meaningfully different safety considerations with the systemic agent versus the other approaches that are directly administered to the CMS.

Yes, Thanks, Eric Thanks for the question. So as you know we're actually right. We are through a pseudo Exxon able to promote the reduction of the Huntington's protein I think it is widely believed that one can see our fee by reducing the approximately 50 per se. We're able obviously the go are lower it's both.

Wild type and mutant forms of that.

And so, but we think that one could certainly establish it or a knockdown of 50% without having any detrimental or toxicity. We said I think what we are all believe is true and we'll be able to monitor that as well. So I think that's that's where we are within our thinking of BNS of what we'll be able to do in terms of the clinic to be able to get at least a 50% reduction.

Got it Thats helpful and maybe just a follow up here if I could on resin plan it sounds.

From Roche's commentary earlier and also on your PR Tonight that.

Unknown Executive: Thanks.

Eric William Joseph: Yeah, thanks, Eric. Thanks for the question.

And then a filing would be contingent on at least some parts of the parts you.

Unknown Executive: So, as you know, actually, right, we are, through a pseudo-exon, able to promote the reduction of the Huntington's protein. I think it's widely believed that one can see efficacy by reducing it by approximately 50%. We're able, obviously, to go lower. It hits both wild-type and mutant forms of that. And so, but we think that one could certainly establish a knockdown of 50% without having any detrimental toxicity. At least that's what I think we all believe is true. And we'll be able to monitor that as well. So, I think that's where we are in our thinking of what we'll be able to do in terms of the clinic to be able to get at least a 50% reduction.

Part two data from the ongoing studies.

Can you clarify whether you may as interested in RTT different both SUNFISH and fire fish or are they prioritizing one and I guess as it relates to the SUNFISH can you just talk little about your expectations for the randomized portion of that study.

What Magnus Fyhr magnitude benefit in an attempt 32. The trial is powered to detect and what would be viewed as regarded as clinically meaningful sure.

Yes, so yes, I think as as Roche has recently discussed and actually in recent interactions with the May that there was a change of heart and that they wanted to see part through a both buyer fish and SUNFISH. So that even as we said previously the fire. The census data centers data will be completed by the end of this year that study as well as the firefighters early next year of that data then will be compiled there was no change.

Eric William Joseph: And maybe just a follow-up here, if I could, on resupplement. It sounds from Roche's commentary earlier and also on your PR tonight that an MAA filing would be contingent on at least some part of the Part 2 data from the ongoing studies. Can you clarify whether EMA is interested in Part 2 data from both Sunfish and Firefish, or are they prioritizing one? And, as it relates to Sunfish, can you just talk a little bit about your expectations for that project?

Just to be clear from any discussions from the FDA in terms of putting in based on part one for both buyer efficient SUNFISH and Mercer you want to take that sure sure and just just to clarify right Eric to answer your questions. So we expect both.

Submissions to two includes other submissions include both our Q4 sufficient fire fish. The main reason on the discussions with the amazed just how close to the completion of the trial as it is.

Unknown Executive: Unknown Speaker Sure, yeah, so I think, as Roche has recently discussed and actually in recent interactions with the EMA, there was a change of heart, and that they wanted to see part two of both firefish and sunfish. So, you know, as we said previously, the sunfish data, the sunfish data will be completed by the end of this year, and that study, as well as the firefish early next year, all that data then will be compiled. There was no change, just to be clear, from any discussions from the FDA in terms of putting in a ban based on part one for both firefish and sunfish.

So they just want to make sure that they see the data. So nothing really unusual here I would say in terms of the power of that trial onshore question.

So.

Just to remind is a two to one randomization originally planned to 186 patients.

The.

Expected point estimate chains are between placebo and the active armed was three points with a sex dissent remediation so half.

Stan the rise measured there this is less than what we've seen in the part one if you were to look into that change compared to natural history. So we feel really good since this group is expected to be less at their genius than the original group was.

Marcio Souza: And Marcia, you want to take this? Unknown Speaker Sure, sure. And just to clarify, in response to your question, we expect both submissions to be completed by the end of this year.

In the in the part one of that trial and we're seeing such impressive results. So far so we feel like quite positive about their results.

Great great. Thanks for taking the question guys. Thank you.

Thank you. Our last question comes from the line of Joseph Stone of Cowen and company.

Marcio Souza: to include, or the submission to include both PAR-204 Sunfish and Firefish. The main reason for the discussions with the M.A. is just how close to the completion of the trials it is. So they just want to make sure that they see the data. So nothing really unusual here, I would say. In terms of the power of that trial to your question, so just to remind you, it's a 2-to-1 randomization originally planned for 196 patients. The expected point estimate change between placebo and the active arm was 3 points with a 6 standard deviation, so a half standardized measure there. This is less than what we've seen in Part 1, if you were to look into the change compared to natural history. So we feel really good since this group is expected to be less heterogeneous than the original group was in Part 1 of the trial, and we've seen such impressive results so far, so we feel quite positive about the results.

Your line is open.

Hi, there. Thank you for taking my questions and congratulations on the quarter.

First on Translarna in Brazil, I was curious if you can give us a little bit more information maybe on ordering patterns, there and the size of those orders.

There was a posting online suggesting the size is around 45 million.

Can you give us any indication on how this is going to be booked and maybe the frequency there and then second on really the plan.

For the initial data from the Rumble fish study are the FDA.

Well they have to receive some of these data and do you anticipate pre symptomatic infants may be able to be on.

The initial labels either in the U.S. for the EU. Thanks.

Greg Murphy authentic for first saw always starts a little bit on the pattern than they use in Brazil and may be Emily can talk a little bit about the revenues right. So.

The dispense is based on the patient consumptions and the amount of patients that are being accrued as Emily mentioned and I mentioned in my remarks as well.

Operator: Great, great. Thanks for taking the questions, guys.

Operator: Thank you.

Operator: Thank you. Our last question comes from the line of Joseph Thome of Cohen & Company. Your line is open.

This is for the clearance patients it's being practice in Brazil that see the minister of health does dispensed to patients that are accrued throughout the year. So we expect that potentially some of those patients are going to receive and add new requests are going to be made periodically I think what it does to US is like that is there is one shipments that was made this quarter, we expect that wouldn't have new shipments.

Joseph Patrick Schwartz: First, on TransLarna in Brazil, I was curious if you could give us a little bit more information, maybe on ordering patterns there and the size of those orders. There was a posting online suggesting the size was around 45 million. Can you give us any indication of how this is going to be scheduled and maybe the frequency there? And then second, on RISDAPLAM, for the initial data from the Rainbow Fish Study, will the FDA receive some of these data? And do you anticipate pre-symptomatic infants may be able to be on the initial labels either in the U.S. or the EU? Thanks.

It is very hard to some extent for us to anticipate is going to be during Q3 or the beginning of Q4, but we know for sure that it is required to be down during this year since the patients use which has been pretty good in terms of compliance they're going to require audio are there to be in terms of the amounts of the shipments and the revenue recognition going to handle to you to emulate you answer. Thanks nice areas were grateful to be in a position of having now a formal approval from the regulatory authorities in Brazil, and now an annual contract really demonstrates the Brazilian government recognizes the benefit for nonsense mutation DMD patients.

Marcio Souza: Great. Marcia, do you want to take that first?

Marcio Souza: Yeah, so I'll start a little bit on the pattern that they use in Brazil, and maybe Emily can talk a little bit about the revenues, right? So the dispensing is based on patient consumption and the amount of patients that are being accrued. As Emily mentioned, and I mentioned in my remarks as well, this is for the current patients. It's being practiced in Brazil that the Ministry of Health does dispense to patients that are accrued throughout the year.

There is an annual contract that we have now entered and if you remember historically, we received a large order for Translarna in Q4, 2018, which reflected fed me for a number of months patients and subsequently did not receive an order in Q1. So a large segment of the annual contract was booked in Q2 and the remainder will be booked in the second half of 2018. This gives us confidence as I mentioned before to reiterate our DMD franchise guidance.

Marcio Souza: So we expect that potentially some of those patients are going to receive them, and new requests are going to be made periodically. I think what it does for us is like there was one shipment that was made this quarter. We expect they're going to have new shipments. It is very hard, to some extent, for us to anticipate if it's going to be during Q3 or the beginning of Q4, but we know for sure that it is required to be done during this year since the patient's use, which has been pretty good in terms of compliance there, is going to require all the orders to be. In terms of the amounts of the shipments and the revenue recognition, I'm going to leave that to Emily to answer.

And then to your second question on the label for car is the plan. So the availability of data in terms of pre symptomatic and whether or not that is going to be included is gonna depends obviously on the amount of babies that are enrolled on the trial between now and the submission on the availability of data and the discussions with the agents during the review so it would be premature probably responsible for us as well two comments. There is right now until we have that's what we know and the discussions that did happen with the FDA is that the label would be based on review of the clearance data for type one two and three which you consider acquiring part and since the IPO and three is our vastly under treated globally and we see the differentiated profile offer is a plan on those patients and in overall I believe and we all hear our concur and sold as the community that there is fewer remaining.

Emily Luisa Hill: Thanks, Marcio. Yes, we're grateful to be in a position of having now formal approval from the regulatory authorities in Brazil and now an annual contract. It really shows that the Brazilian government recognizes the benefit for non-transmutation DMD patients. There is an annual contract that we have now entered into, and if you remember, historically, we received a large order for translarna in Q4 of 2018, which reflected the need for a number of months for patients and subsequently did not receive an order in Q1. So a large segment of the annual contract was booked in Q2, and the remainder will be booked in the second half of 2019. This gives us confidence, as I mentioned before, to reiterate our DMD franchise guidance.

And may be growing unmet needs on type ones, considering the market dynamics that are happening every day.

Great. Thank you.

Thank you at this time I'd like to turn the call back over to CEO Stuart Peltz for closing remarks, Sir.

Okay, well. Thank you all for joining the call today as you can see the team has been executing quite well I'm very proud of what they've been able to get accomplished in this half year I think it's really important for all our stakeholders to continue the build out the company that we talked about and it's gratifying to see the execution on the vision ability now to have over disorders company. So thank you for joining the call.

Emily Luisa Hill: And then to your second question on the label for the RISA plan, so the availability of data in terms of pre-symptomatic and whether or not that's going to be included, it's going to depend obviously on the number of babies that are enrolled in the trial between now and the submission on the availability of data and the discussions with the agents during the review, so it would be premature, and probably responsible, for us as well, to comment on this right now until What we know and the discussions that did happen with the FDA is that the label would be based on a review of the current data for type 1s, 2, and 3, which we consider quite important since type 2 and 3s are vastly undertreated globally, and we see the differentiated profile of RISA plan in those patients. And overall, I believe, and we all here concur, and so does the community, that there is still a remaining and maybe growing unmet need for type 1s considering the market dynamics that are happening every day. Great, thank you.

Thank you, Sir ladies and gentlemen that concludes today's conference. Thank you for your participation you may disconnect your lines at this time.

Have a wonderful day.

Marcio Souza: Thank you. At this time, I'd like to turn the call back over to CEO Stuart Peltz for closing remarks.

Unknown Executive: Okay, well, thank you all for joining the call today. As you can see, the team has been executing quite well, and I'm very proud of what they've been able to accomplish in this half year. I think it's really important for all our stakeholders to continue to build out the company that we talked about, and it's gratifying to see the execution and the vision of building out a rare disorders company. So, thank you for joining the call.

Operator: Thank you, sir. Ladies and gentlemen, that concludes today's conference. Thank you for your participation. You may disconnect your lines at this time. Have a wonderful day.