Q3 2019 Earnings Call

Ladies and gentlemen, thank you for standing by and welcome to the PTC Therapeutics 2019 third quarter corporate update in financial results.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the PTC Therapeutics 2019 3rd Quarter Corporate Update and Financial Results. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero.

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

After the speaker presentation, there will be a question and answer session.

Ask a question during the session you would need to press star one on your telephone.

Please be advised to today's conference is being recorded.

Required any further assistance please press star zero.

Unknown Attendee: I would now like to hand the conference over to your speaker today, Alex Cain, Head of Investor Relations. Thank you. Please go ahead, sir.

I'd now like to handle the conference over to your speaker today, Alex King.

Investor Relations. Thank you. Please go ahead, Sir Thank you Hello, everybody.

Unknown Attendee: Thank you. And Hello, everybody. Good afternoon. Thank you for joining us to discuss our 2019 Third 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, 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 statement. 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 to non-GAAP is available in today's earnings release. With that said, let me pass the call over to our CEO, Stuart Peltz.

Good afternoon. Thank you for joining us to discuss our 2019 third quarter corporate updates and financial results. Joining me on today's calls our CEO Stuart Peltz, our Chief operating Officer, Marcial, 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 actually.

Dictation.

Please take a moment to review our slide on or simultaneous presentation, which contains our forward looking statements.

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

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

We will disclose certain non-GAAP information during this call information regarding our use of GAAP and non-GAAP financial measures at 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.

Unknown Executive: Thanks, Alex. Thank you for joining us this afternoon as we provide an update on the third quarter. As you heard, on the call with me today will be our COO and CFO, Marcio, and Emily. Marcio will provide commercial and clinical development updates. Additionally, Emily will provide an update on our Q3 financial results. In this quarter, we have continued to advance our mission of creating a diversified, fully integrated biotech company with multiple platforms. As we have previously described, our strategic vision is to be a leading diversified rare disorder company that, through the combination of both using our internal innovative scientific platforms, as well as business development, we will have multiple products and programs and anticipate approximately $1.5 billion in revenue by 2023. Today, we will continue to discuss our efforts in building out this vision of the company and how we are executing it across a number of programs.

Thanks, Alex Thank you for joining us this afternoon.

Provided an update on the third quarter.

Have you heard on the call with me today will be our COO and CFO Marshfield anomaly Marcia will provide commercial and clinical development update. Additionally, unbelievable well provide update on our Q3 financial.

In this quarter, we have continued to advance our mission of creating a diversified fully integrated biotech company with multiple platforms.

And where previously described.

Our strategic vision is to be a leading diversified rare disorder company that through the combination of both usually not only terminal.

The scientific platforms as well as business development, we will have multiple products and programs and anticipate approximately $1.5 billion in revenue by 2023.

Today, we will continue to discuss our efforts Adobe now this vision Oh the company in how we are executing across a number programs. We were also reviewed the results presented during the world muscle Society that highlighted the continued clinical benefits and competitive advantage seen with with the plan.

Unknown Executive: We will also review the results presented at the World Muscle Society that highlighted the continued clinical benefits and competitive advantage seen with RISDA plans. I'm proud to report that in October, TXETI was approved in Brazil by INVISA. Along with TRANSLARNA, this marks the second approval that we have successfully achieved in Latin America this year. The opportunity to treat HATTR in Latin America is important because the disease has a Portuguese Sponger effect. Brazil is the largest country with Portuguese ancestry and one of the largest markets worldwide, with approximately 5,000 patients.

I'm proud to report that in October took seven was approved in Brazil by in visa.

How long would trend, Florida. This marks the second approval that we have successfully achieved in Latin America in this year.

The opportunity to treat H.P.T. are in Latin America is important because the disease has a Portuguese farmers effect.

Brazil, the largest country wouldn't Portuguese ancestry with one of the largest markets worldwide with approximately 5000 patients.

Unknown Executive: Additionally, TXETI has the advantage of being delivered by subcutaneous injection, as infusion centers in Latin America are often saturated or hard to access. Through our early access programs, we are seeing that there is a high medical need in Latin America. We have continued to educate the community on the importance of identifying patients and ensuring that these patients gain access to medicine. The NVISA approval will allow us to initiate TechCity's launch, giving us the opportunity for direct physician outreach. We have also been continuing to grow our D&D franchise. As you will hear about this in more detail, we reported top-line combined commercial revenues of $71.4 million in the third quarter of 2019 when compared to the previous year's third quarter of $53 million.

Additionally, tech savvy have answered being delivered by subcutaneous injection as infusion centers in Latin America, often saturated are hard towards fast.

Early access programs, we're seeing that there was a high unmet medical need in Latin America.

We have continued to educate their community on the importance of identifying patients.

Sure that these patients gain access to Madison.

The NVS approval will allow us to initiate took savings launch, giving us the opportunity for direct physician outreach.

We have also been continuing to grow our DMT franchise as you will hear about this in more detail, we reported topline combine commercial revenues of $71.4 million in the third quarter of 2019, when compared to previous year third quarter of $53 million.

Unknown Executive: We have also shared results from the STRIDE Registry this quarter, which is the first international registry for patients with DMD due to a non-susceptible mutation receiving transluarinase. I'm also pleased to announce that we have acquired a late-stage asset from Bioelectron Technology Corporation that will be integrated into our portfolio. This asset targets a key enzyme involved in the regulation of oxidative stress and inflammation. The compound is ready to be in pivotal trials for select CNS rare disorders and has the potential to be used in combination with existing programs in our pipeline. We have agreed to pay success-based milestones that are due one year after certain regulatory approvals.

We've also shared results from the stride registering this quarter, which is the first international registry for patients with DMT due to a nonsense mutation receding translarna.

I'm also pleased to announce that we have acquired a late stage asset for bio what front technology Corporation that will be integrated into our portfolio.

This asset targets are key enzyme involved in the regulation of lots of data stressed and inflammation.

The compound is ready to be a pivotal trials for select see this rare disorders and has the potential to be used in combination with existing programs in our pipeline.

We have agreed to pay success based milestones that are doing one year after certain regulatory approvals. We believe this is an exciting opportunities because of the novel approach it pretty rare CMS and anti inflammatory disorders.

Unknown Executive: We believe this is an exciting opportunity because of the novel approach to treating rare CNS and anti-inflammatory disorders. I'd now like to turn to our programs in gene therapy. As we previously mentioned, we are on track to submit a BLA to the FDA by the end of the year for our AADC gene therapy program. I'm happy to report that we have successfully completed the necessary manufacturing run of AADC gene therapy products required for the BLA submission. We also plan to file an MAA in Europe for AADC deficiency following our submission to the FDA. We are proud to potentially be in a position to launch one of the first gene therapy programs worldwide. As Marcia will discuss with you in more detail, we have ramped up our patient finding efforts, and we expect to be in a good position to have a strong launch for this product next year. Meanwhile, our gene theory program in Frederick ataxia continues to move forward.

I'd now like to turn to our programs in gene therapy.

As we previously mentioned we're on track to submit ability to be yesterday by the ended the year for our E. D C gene therapy program.

I'm happy to report that we have successfully completed the necessary manufactured wrong to babysit gene therapy product.

<unk> for the B.L.A. submission.

We also plan to file in EMEA in Europe , or 80 feet deficiency, following our submission to the FDA.

We are proud to potentially being in a position the launch one of the first gene therapy program worldwide.

Marty will discuss with you in more detail, we've ramped up on patient finding efforts and expect to being a good position Denver strong launch for this product next year.

Our gene therapy program with Frederic at Tuxedo continues to move forward. However, because of manufactured timelines. We now expect to enter the clinic mid next year.

Unknown Executive: However, because of manufacturing timelines, we now expect to enter the clinic mid-next year. Let me now switch gears to update you on the progress we have been making using our splicing platform. Our collaboration with Roche and the SMA Foundation on RISDAPlan for the treatment of SMA is progressing very well. Recently, we shared updated clinical information from the pivotal Firefish and Sunfish studies. At the World Muscle Society meeting, we reported that SMA patients demonstrated continued improvement, including observing babies that are beginning to walk and stand. These are milestones that would otherwise not have been achieved.

Let me now switch gears to update you on the progress we've been making using our splicing platform.

Collaboration with most of the SMB Foundation en route to plan for the treatment of estimate is progressing very well.

Recently, we sure update updated clinical information from the pivotal bio fish and Sun for studies at the World Muscle Society meeting, we reported that actually make they should demonstrated continued improvement, including observing babies that are beginning to walk ins Dan.

These are milestones that would have otherwise not have been achieved.

Unknown Executive: Additionally, RISDA plan continues to be well tolerated with no dropouts reported from adverse events. Given that RISDaplans has been studied in a broad cohort of SMA patients, we would expect a potential approval to be for a broad label to include all SMA patients for a launch next year. The importance of the SMA program is that it is the first small molecule drug that is orally bioavailable, that is systemic, that goes to all tissues affected that lack the SMN protein. This is the first small molecule that has been shown to be selectively affecting splicing and leads to modulating gene expression, therefore validating our splicing platform. We anticipate this to be widely used in all types of SMA patients. Based on the success of this program, we have used our platform to identify other splicing modulators that affect splicing to treat other diseases. In particular, we have discussed two programs that have identified molecules that selectively and specifically impact splicing that have the potential to treat orphan disease disorders. One compound was identified to treat patients suffering from milial dysautonomia, or FD, and the other program is to treat patients suffering from Huntington's disease, or HD. I will now discuss these programs in more detail.

Additionally reached the plant continues to be well tolerated with no drop off reported from adverse events.

Given that discipline has been studied in a broad cohorts of estimate patience, we would expect a potential approval to before a broad label to include all lessen the patients for a launch next year.

It's important to the estimate program was was that as the first small molecule drugs that is orally bioavailable that a systemic the goes to all tissues affected that left be asked them and protein. This is the first small molecule that has been shown to be selectively affecting spicy and leads to modulating gene expression. Therefore.

Validating our splicing platform.

We anticipate this to be widely used in all types of so many patients.

Based on successful. This program, we have you done platform to identify other spicy modulators that affects flight seemed to treat diseases. In particular, we have discussed two programs that have identified molecules that selectively specifically impacts flexing that have the potential for orphan disease disorders one.

Compound was identified to treat patients suffering from million just ought to know meal or F.D. and the other programs the treat patients suffering from huntingtons disease or H D. I will now discuss these programs.

Unknown Executive: PTC258 is an orally bioavailable, highly potent splicing molecule that has been shown to effectively correct the splicing defect in FD. This is an ultra-orphan disorder with a small patient population of only a few hundred patients in the U.S. and Israel, resulting from a founder's mutation predominantly found in Ashkenazis. Jewish Population, The FDA recently indicated that the clinical development path of FD would require a long and complex two-year or greater placebo-controlled trial. This trial design is not feasible in this small patient population. At this point, there is not a development path that allows us to move forward in FD. Unfortunately, in drug development, we have to make difficult decisions, and as such, we have discontinued this program. We are disappointed for the patients and their families that suffer from familial dysautonomia.

Do you see 258, as an orally bioavailable highly potent splicing molecule that has been shown to effectively correct displacing to factor in ft. This is an ultra orphan disorder with a small patient population of only a few hundred patients in the U.S. and Israel, resulting from a found visitation predominately founder Gostin Odyssey.

Jewish population.

The F.D.A. recently indicated that the clinical development path of Ft would require a long and complex two years or greater placebo controlled trial.

This trial design is not feasible in the small patient population.

This point, there's not a development path that allows us to move forward enough D. Unfortunately in drug development, we have to make difficult decisions and as such we have discontinued. The program. We are disappointed that for the patients and their families that suffer from familiar to us on inovio.

Unknown Executive: We will continue to work with the rare disease community to advocate for the regulatory process that would allow for ultra-rare disorders and difficult diseases to move forward. Let me now switch to discuss our HD program. We are highly focused on rapidly advancing our Huntington's program. The compounds identified are exciting and have shown to be selective splicing modifiers and shown reduction of the HDT protein in all areas of the brain, as well as other tissues in the HD mouse model.

We will continue to work with the rare disease can you repeat the advocate for record for the regulatory process that would allow for ultra rare disorders in difficult diseases to move forward.

Let me now switch to discuss our H.D. program, we're highly focused on rapidly advancing our Huntingtons program.

The compounds identified our exciting have shown to be selective splicing modifiers and shown reduction of the H.T.T. protein in all areas of the brain as well as other tissues in the HD mouse model. We are now when the process of performing larger scale GMP production of one each day.

Unknown Executive: We are now in the process of performing larger-scale GMP production of one HD compound to perform GLP safety toxicology. As the program is advancing rapidly, we continue to expect that the Huntington's Disease Program will enter the clinic in 2020. Like SMA, there are a number of advantages to having an orally bioavailable compound that is systemically delivered through the blood and has broad distribution to tissues, including all tissues in the brain. We believe that a therapeutic that is systemic and simple to deliver will bring a strong competitive advantage to the huntingtins disease landscape. As you can see, we have a number of exciting milestones coming up. We will be hosting an analyst day on March 5th, and we look forward to sharing more detailed information on our pipeline at that time. I'd like to turn the call over to Marcio so he can provide an update on the commercial clinical development programs at PTC.

Compound to perform GLP safety toxicology.

As the programs advancing rapidly we continue to expect that the Huntingtons disease program well into the clinic in 2020.

Like estimate there are number of advantages and having an orally bioavailable compound that is systemically delivered through the blog and as broad distribution to tissues and including all tissues in the brain, we believe that a therapeutic that a systemic and simple to blow up or will bring a strong competitive advantage to the.

On teams loot tons disease Lionsgate.

You can see we have a number of exciting milestones coming up.

We will behold, we will be hosting an analyst day on March 5th and we look forward to sharing more detailed information on our pipeline at that time.

I'd like to turn the call over tomorrow. So it can provide an update on the commercial and clinical development programs that P. do fee Marcio, Hey, Thanks to let me start to color Jim get franchise.

Marcio Sousa: Thank you.

Marcio Sousa: Hey, thanks, too. Let me start with our DMD franchise. MFLAZA, our treatment approved for all DMD patients 2 and older in the U.S., reported revenues of approximately $68 million year-to-date. In the third quarter, we saw strong prescription growth. However, net sales were impacted primarily by two factors. The first related to our special pharmacy transition to a credo, where we faced challenges while processing all the new case transitions. We have completed the transition, and we do not expect to have any further impacts in the following quarter. The other factor that affects net sales was the mix of Medicaid's utilization. This drove us to make a change in our growth-to-net assumptions in order to align with our expected private-to-public-payer mix both now and in the future, at the Market Access Forum. We have been working diligently to educate payers on the benefits of Enflasa. Recently, we have seen an improvement in the conditions by which some important plants are operating, including removing requirements for presence-zone treatment as an added step.

And plaza or treatment approved for all DMD patients you wouldn't older in the last reported revenues of approximately $68 million year to date.

The third quarter, we saw strong prescription growth how ever been that see us warding back to primarily by two factors.

The force related to our specialty pharmacy transition to Accredo why do we face challenges while processing all the new case conditions.

We have completed the transition and we do not expect to have any forward it impacts in the following quarters.

The other factors FX net sales was the mix up Medicaid localization.

This drove us to make a change in our girls to map assumptions in order to align with our expected private to public payer mix, both now and the future.

In the market access drones.

Have been working diligently to educate figures on the benefits up and plaza.

Recently, we have seen improvements into conditions by which some important plants are operating including removing requirements for pride in its own treatments as a stab at it.

Marcio Sousa: To further demonstrate MFLASA's benefits, during WMS, data collected from Cincinnati children on more than 400 GMD boys was presented. This data showed clear motor and pulmonary benefits of emphasa when compared to other corticosteroids. This is one of the largest cohorts ever observed and studied in GMD. The data reinforce the importance of correct use of steroids in the management of this disorder, and you continue to work with physicians and payers to understand the benefits of Enflaza. Now I'm switching gears to TransLearner.

To further demonstrate can fathers benefits during WMS data collected at Cincinnati childrens on more than 400, DMD boys watts present that.

This data show clear motor implement our benefits off in Sasa when compared to other corticosteroids.

It is one of the largest cohorts apple or observed any studied in PMT.

The data reinforce the importance of correct use a fair right you didn't management this disorder.

Do you continue to work with physicians and payers to understand the benefit than plaza.

Now switching gears to Translarna.

Marcio Sousa: We have seen a strong year-to-date performance with revenues of approximately $141 million. We continue to see growth in demand and support from physicians and patients in all territories where TransLerna is available, and we continue to execute on our geographic expansion. Most recently, with the addition of a PTC subsidiary in Russia, which we believe will enable growth in the region. In addition, as Stuart mentioned, we're excited about the body of evidence supporting Translearners' effectiveness, including the data coming from the first Duchenne product registry, STRIDE, which is following up more than 200 patients with non-sense mutation DMD who are receiving TransLerna globally. We reported real-world long-term evidence from TransLerna-treated patients coming from this registry. The data shows that long-term treatment with TransLerna slows disease progression by preserving both pulmonary and motor function in all patients observed in the registry. As you know, patients die due to respiratory and cardiac failure.

I've seen a strong year to date performance with revenues up approximately $141 million.

We continue to see growth in demand in support from physicians and patients in all territories Translarna is available.

And we continue to execute our geographic expansion. Most recently with addition of happy to see subsidiary in Russia, which we believe we were unable to grow in the region.

In addition, as Stuart mentioned, we're excited with the body of evidence supporting Translarnas effectiveness, including the data coming from the forced motion products registry strike.

Just following up more than 200 patients with nonsense mutation DMD.

Who are receiving translarna globally.

We reported to reward long term ABS Dan.

From Translarna treated patients coming from these rats history.

The data shows that long term treatment with Translarna is low disease progression by preserving bowl pulmonary and motor function in all patients observed undergraduates three.

As you know patients die due to respect our in cardiac failure.

Marcio Sousa: In these cohorts, we observed that 32% of patients receiving standard of care had an FVC of less than 50%, which is in line with the decline in lung function expected in this disease, and it compares with only 2.2% of patients who received TransLerna achieving such milestones. Additionally, patients receiving TransLerna had a prolonged ability to withstand transupine for three years when compared to untreated patient populations. Continuing with our commercial portfolio, we're happy to have received regulatory approval by INVISA for tax credit this week, an important milestone which enabled pricing registration and negotiations with the Brazilian government to make TaxSetti available to all patients who may benefit in the country. We've had this team in place for market development and medical support since the beginning of this year, and now intends to start launching activities for TEC-SETI immediately in Brazil. We are proud to add this important regulatory approval and are committed to serving all the patients in need in Latin America. Our next major regulatory step in the region is to file for the approval of Wai Livra.

In this cohorts, we absorb that 32% of patients receiving standard of care has done that you see a flat and 50%.

Which is in line with the decline in lung function expected in this disease.

And he compares with only 2.2% of patients who receive translarna achieving such milestone.

Additionally, patients receiving translarna had a prolonged ability we stand sounds supine like three years when compared to one three that patient population.

Continuing with our commercial portfolio, we're happy to have received regulatory approval by MTS apart that said the deadweight.

Then important milestone, which enabled pricing registration in negotiations with the President Bob Herman.

To make that Saudi available to all patients who may benefit in the country.

We had that seeming place for market developments in medical support since the beginning of this year.

And now intends to start launching activity for tech savvy immediately in Brazil.

We are proud to ads is important regulatory approval.

Committed to serve all the patients in need in Latin America.

Our next major regulatory staffing division is to file for the approval walkway Libra.

No focusing on agency deficiency.

Marcio Sousa: Now focusing on the ADC deficiency, we are preparing for a successful launch in the United States next year with the expected FDA submission this quarter and subsequent approval in 2020. Market preparation is well underway with a clear plan to cover both the prescribing population and the centers of excellence conducting the neurosurgical procedure. In terms of patient finding, our approach involves multiple channels. First, our field-based personnel are distributing, at no cost, testing kits to any clinicians that suspect an ADC-deficient patient within their practice.

We are preparing for a successful launch and United States next year with expected ft. A submission this quarter and subsequent approval into went to 20.

Markets preparation is well underway, we've got clear plan took over both the prescribing population.

But also the centers effects on on conducting dinner surgical procedure.

In terms of patient finding our approach involve multiple channels.

First our field based personnel are distributing at no cost.

I think it's for any clinicians that suspects an agency deficiency patients within their practice.

A protocol driven broad based screening Prague himself cerebral palsy is also advancing.

Marcio Sousa: A protocol-driven, broad-based screening program for cerebral palsy is also advancing, and our social media initiatives have launched with a good success rate today. Additionally, we have recently established a partnership that would add ADC deficiency to a second-tier newborn screening panel in the United States, and we are working together on the task validation. We expect more than 200,000 babies to be screened at birth for ADC deficiency next year, and more than a million in 2021. Our goal is to have more than 300 addressable patients available before launch to be converted to commercial in key territories. We are on track to reach that goal.

In our social media initiatives have launch with good success rate to date.

Additionally, we have recently established a partnership.

Which would add aid to see the efficiency to a second tier newborn screening panel in the United States.

And we are working together on this past validation.

We expect more than 200000 babies to be screen at bar for agency deficiency next year in more than a million into went its went to one.

Our goal is to have more than 300 addressable patient available before launch to be converted to commercial empty territories.

We are on track to reach that goal.

Turning to our clinical development pipeline.

Marcio Sousa: Turning to our clinical development pipeline, we have completed enrollment in Study 45, which is our Dystrophin Measurement Study in the United States for Translearners. This study, if positive, will serve as the basis for the NDA resubmission in the U.S. We have also had the last patient last visit for our Aniridia study for translearners, which should read out at the beginning of next year. Our Fredericta Taxi Clinical Development Program is progressing well, as we prepare to dose the first patient next year. Lastly, Stu just mentioned we have acquired some assets from Bioelectrum, and we intend to initiate a clinical trial in mitochondrial epilepsy with the most advanced compound early next year. The trial has been designed based on scientific advice received from the European Medicines Agency. We also intend to explore other uses, considering the anti-inflammatory properties of these compounds, which we're going to be disclosing in the near future. I'll now hand the call over to our CFO, Emily Hill. Okay?

We have completed enrollment in study 45.

Which is our dystrophin measurements study in the United States for Translarna.

This study is positive we serve part D N G resubmission anyway.

We have also had the last patient last visit for on the reader study for Translarna, which should read outs at the beginning of next year.

Oh refrigerant attacks it clinical development program is progressing well.

As we prepare to dosed the first patient next year.

Lastly.

Stuart just mentioned, we have acquired some assets from bio lack huh.

We tends to initiate a clinical trial and Michael Kors grip, let's see if with the most advanced compound early next year.

The trial has been designed based on scientific advice received from the European Medicines Agency.

We also intends to explore all do use cost synergy anti inflammatory properties off this compounds, which are gonna be disclosing in the near future.

I'll now hand, the call over to our.

CFO Emily Hill EM.

Emily Luisa Hill: Thanks, Marcio. I also wanted to take a moment to acknowledge a new member of the Investor Relations Team, Alex Kane. Alex comes to us from the agency side and NASDAQ, where he spent almost a decade focused on biotech companies. We are very happy to have him join us at PTC.

Yeah.

Wanted to take a momentous knowledge and new member at the Investor Relations team Alex.

I joined US from the agency side on NASDAQ, where he spent almost a decade focused on biotech company.

We're very happy to have them PTC.

Emily Luisa Hill: As you know, our third quarter press release was disclosed shortly before today's call, which summarizes the details of our financial results. Please see that release for further details. I'll start with a few comments on our financial performance in the quarter and our guidance for the full year 2019. Starting with our top-line results, we reported $71.4 million in combined net revenue across our commercial portfolio in the third quarter of 2019, compared to combined net revenue of $53 million for the third quarter of 2018. TransLarna Net Product revenues were $48.3 million for the quarter. This compares to $30.4 million in the third quarter of 2018. This growth includes the expansion of TransLarna XUS, including regulatory approval and an annual contract with Brazil.

As you know our third quarter press releases disclose shortly before today's call, which summarizes the details of our financial results.

Please see that release for further details.

It was a few comments on our financial performance in the quarter and our guidance for the full year 2019.

Starting with our top line results, we reported 71.4 million in combined net revenue across our commercial portfolio in the third quarter 2019, compared to combine that revenue of 53 million for the third quarter Tony.

Translarna net product revenues were 48.3 million for the quarter. This compares to 30.4 million in the third quarter 20.

This growth includes the expansion of tends line, a at U.S., including regulatory approval and annual contracts in Brazil.

Emily Luisa Hill: For IMSLASA, we reported net product revenues of approximately $22.9 million for the third quarter of 2019, which compares to $22.6 million reported in the third 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.

Well I'm glad that we reported net product revenues of approximately 22.9 million for the third quarter 2019, which compares to 22.6 million reported in the third quarter 28.

We're working towards establishing unpleasant the standard of care for all patients in the U.S. and are happy to be able to bring some plaza Nash patients as young as two years of AIDS.

Operator: Continued growth of the DMD franchise and our annual contract with Brazil for TransLarna give 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 $58.1 million for the third quarter of 2019, excluding $5 million in non-cash stock-based compensation expense, compared to $49.9 million for the third quarter of 2018, excluding $4.4 million in non-cash stock-based compensation expense. The increase in R&D expenses reflects our strategic investment in advancing the gene therapy platforms, splicing programs, and other research programs, as well as the advancement of the Non-GAAP SG&A expenses were $43.8 million for the third quarter of 2019, excluding $5.5 million in non-cash stock-based compensation expense, compared to $33.9 million in the third quarter of 2018, excluding $4.5 million in non-cash stock-based compensation expense.

Continued growth of the DMD franchise, and our annual contracts with Brazil for Translarna give us confidence to reiterate our 2019 Dnbi franchise revenue guidance.

85 to 305 million.

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

non-GAAP R&D expenses for 58.1 million for the third quarter 2019, excluding 5 million a noncash stock based compensation expense compared to $49.9 million and third quarter 28, excluding 4.4 million in noncash stock based compensation.

The increase in R&D expenses reflect our strategic investment in advancing the gene therapy platforms leasing programs and other research programs as well the advancement of the clinical pipeline.

non-GAAP .

Expenses for 43.8 million for the third quarter 2019, excluding 5.5 million a noncash stock based compensation expense compared to 33.9 million in the third quarter 2018, excluding 4.5 million in noncash stock based compensation expense.

Operator: Reflecting continued investment in support of our commercial activities, launch preparedness in Latin America, and global patient finding efforts. I would also like to update non-GAAP, R&D, and SG&A expense guidance for full year 2019 to $380 to $390 million, excluding non-cash, stock-based compensation expense of approximately $40 million. An increase from $360 to $370 million, excluding activated non-cash stock-based compensation expense of approximately $35 million. This increase in operating expense is due primarily to business development activities and investment in gene therapy manufacturing. The net loss for the third quarter of 2019 was $60 million, compared to a net loss of $51 million for the third quarter of 2018. Cash, cash equivalents, and marketable securities totaled $708.6 million on September 30, 2019, compared to $227.6 million on December 31, 2018.

Reflecting continued investment in support of our commercial activity on preparedness, and Latin America, and global peace and timing.

I'd also like to update non-GAAP , R&D and I've seen a expense guidance for full year 2019 to 380 390 million, excluding noncash stock based compensation expense approximately 40 million.

An increase from 363 70 million excluding after they didnt noncash stock based compensation expense of approximately 35 million.

This increase in operating expenses due primarily to business development activities and investment and gene therapy manufacturer.

Net loss for third quarter, 2019 was 60 million compared to net loss of 51 million for the third quarter of 20 team.

Cash cash equivalents and marketable securities totaled 708.6 million at September Thirtyth 29.

Compared to 227.6 million at December 31st 2018.

Operator: In September, we completed a financing that amounted to $287.5 million in convertible bonds and $100 million in equity for a total consideration of $387.5 million, resulting in net offering proceeds of approximately $376 million. This financing puts us in a strong position to execute on many fronts towards achieving our $1.5 billion 2023 revenue target. Operator.

In September we completed a financing that amounted to 287.5 million convertible bonds and 100 million an equity for total consideration of 387.5 million, resulting in net offering proceeds of approximately 376 nine.

This financing puts us in a strong position to execute on many fronts towards achieving our 1.5 billion 2023 revenue target.

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

Operator.

Operator: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Alethea Young from Cantor.

Thank you as a reminder to ask a question you would need to press star one on your telephone.

You are your question press the pound key.

Please standby wobble compiles acuity roster.

Our first question comes from a leap year young from Cantor. Please go ahead.

Unknown Attendee: Please go ahead. Hey guys, thanks for taking my question and congrats on all the progress. Maybe two for me. Just one, I feel like you snuck in this BioElectron.

Hey, guys. Thanks for taking my question Congrats on all the progress maybe two for me just one I feel like you snuck in this I buy electronics I was looking on the spot on the on the website are you guys kind of using the <unk> 7.3, like and using the same combination other assets I guess, maybe can you talk a little bit more in detail as it relates to your platform I'm not sure. If it's too early and then.

Unknown Executive: I was looking on the website. Are you guys going to be using this EPi 743 and using this in combination with other assets? Maybe you could talk a little bit more in detail as it relates to your platform? I'm not sure if it's too early. And then on the second side of things, I wanted to check on the USDMD study, which sounds like it's still being read out sometime relatively soon. And I guess, how are you thinking about potentially filing? I know some people have paid attention to what happened with Sarepta in the case of Goldursun. Do you feel confident in the agreement you have with the FDA around Distrofen here at this point? Thank you.

Second side of things I wanted to check on the U.S. DMD study, which it sounds like it's still reading out sometime relatively soon and I guess, how are you thinking about potentially filing I mean, I know some people are paying attention to what's happened with like you know syrup. Then the case. Some golodetz then I mean do you do you feel confident in the agreement and what you have with the FDA around dystrophin here at this point. Thank you.

Unknown Executive: Hey, thanks, Alicia, for the question. Yeah, BioElectronite, we thought, was a very interesting company with a strong scientific platform that targets oxidative stress and redox. And this turns out to be quite important for mitochondrial function and neural inflammation or inflammation in general. And so we were very excited about it. And the EPI 743, as you see, is their most advanced program that we think is, in a sense, a PIVL-ready program, study-ready for potentially a number of different disorders.

Yeah, I think solutions for the question Yeah bio electronic we thought was a very interesting company with a.

Strong scientific platform that hit oxidative stress every dark.

And this turns out to be quite important vermonter comp mitochondrial function and neural inflammation or inflammation in general.

And so we were very excited about it and appease 743 as you see is there most advanced programs that we think is.

Pivotal ready program, a study regnery for for potentially a number of different sorry, maybe I haven't Martha will talk a little bit above that but that's what we thought was really quite excited or what we're gonna be focused on <unk>.

Unknown Executive: And maybe I'll have Marcia talk a little bit about that, but that's what we thought was really quite exciting and what we're going to be focused on. And as I talked about in the script originally, this is really a success base. We're excited. We think it's a very important asset that can complement not only new diseases but can work in inflammation, and we can explore it in other diseases like DMD as well. So we're excited about that. Marci, you want to talk about that? Absolutely, Stu. And thanks, Alicia, for the call. So first and foremost, I'm going

Well I talked about in the script. Originally this is really Oh success based.

Milestones the two on success of of the of approvals on trials than before so we're excited we think it's a very important.

Assets that can complement not really new diseases, but couldn't work in inflammation. We can explore another diseases like BMT as well. So we're excited about that most of you want to talk about yeah. Absolutely. Soon thanks, Alicia for sort of call. So first and foremost sorry extremely excited just to just adds about brings.

Marcio Sousa: So, we're extremely excited, as Zistu just said, about bringing the portfolio here through these asset agreements with Bioelectron. Specifically, I wanted to call out that some of the team members are coming as well and are joining PTC. I'm especially proud to have Matt Klein, who is now the CEO of Bioelectron, joining the team and leading the efforts with 743 and other assets here. We're going to be focusing on some of the diseases I mentioned in my prepared remarks. The first one is mitochondrial epilepsy.

In the portfolio here for this asset agreements with five elektron.

Specifically I wanted to call outs that some of the team members are coming as well in our joining b to C.

I'm, especially proud to have Matt Klein, who is the CEO now by electrum, joining the team and leading the effort to seven for three and other assets here, we're going to be focusing on some of the disease as I mentioned on my prepared remarks. The first one is mitochondria lapses.

Marcio Sousa: We see a very high unmet need there, several thousand patients in the U.S., several thousand patients outside of the U.S., so a relatively large market opportunity, but yet a relatively small clinical trial to get to development, very interesting phase two proof of concept already in-house with this. So we're going to move that quickly and then go for a very rigorous process to prioritizing the other indications to see what makes sense. Obviously, inflammation is at the core of a lot of the things we do right now, like DMD, and you're going to take a look and see what really matters in terms of patients and whether or not we should move forward in other indications as well.

We see a very high unmet needs there several thousand patients in the last several thousand patients outside of the west so relatively large market opportunity, but yes relatively small clinical trials forgot to developments very interesting phase two proof of concept already in house.

With that so we're going to move that quickly and then going to go for a very rigorous process to prioritizing. The other indications just see what makes sense, obviously inflammations into core if a lot of the things we do right now like DMD and you're going to take a look and look at what really matters in terms of patients and and whether or not.

It should move forward and other indications as well.

Marcio Sousa: And then in terms of the DMD, you know, we're pretty confident we had long discussions with Janet Woodcock about what was required. And just to remind you that anything above background with the clinical data that we currently have on hand should be sufficient for approval. So we've had substantial discussions and feel comfortable that we have an agreement to move forward based on that.

And then in terms of the DMD.

Yeah, we're pretty confident we had long discussions were Janet Woodcock on what was required and just to remind you that it was anything above.

Background with the clinical data that we currently have on hand, Oh should be sufficient for approval. So we've had.

Substantial discussions or feel comfortable that we have an agreement to move forward based on that.

Great. Thanks.

Unknown Executive: Great, thanks. Thank you. Our next question comes from Vincent Chen from Bernstein. Please go ahead. Good, congratulations.

Yep.

Thank you.

Next question comes from Vincent Chen from Bernstein. Please go ahead.

Hey, congratulations thanks for taking the questions a couple of them on the Huntingtons disease program.

Operator: Thanks for taking the questions. A couple of them on the Huntington's disease program. First, I was wondering if you could provide some detail on what are some of the assays that you use to assess the risk of off-target splicing in different cell types and so forth. What preclinical studies are the potential candidates subjected to? And I would guess, which of these have been completed to date? What remains to be done on this front?

First I was wondering you can provide some detail on what are some of the assays that you used to assess the risk of off target slicing.

In different cell types, and so forth, what preclinical studies already potential candidates subject to and I guess, which of these and complete a date what remains to be done on this front and then secondly, how do you think about the target product profile you'd be aiming for in particular.

Vincent Chen: And then secondly, how do you think about the target product profile you'd be aiming for? In particular, I guess, if you think about it, you've shown pretty substantial knockdown in the preclinical studies. What level of knockdown would you be looking to target in a clinical program?

I guess, if you think about you've shown pretty substantial knock down the preclinical studies what level knocked down would you be looking to target in a in a clinical program.

Unknown Executive: Sure, thanks for that. And so, in general, we use, in a sense, a chemical genomics approach in terms of identifying molecules first in a high-throughput screen and then going into cell and animal-based molecules. And they're always counterscreened against a number of other similar, yet not identical, splicing events to watch. And so we look very carefully at that as well. Then we also use, in a sense, safety toxicology as an important measure as well, because at the end of the day, whether it's on-target or off-target, we tend to want to find that out. So this happens quite early within our screening tier.

Sure Thanks for that and so you're in general our approach is really we used in the sense a chemical genomics approach in terms of identify molecules first at a high throughput screen and I go read it to sell in animal base molecule and they're always counter screens against a number of other what we think are similar.

Oh, yes, not identical splicing events to watch and so we look very carefully at that as well then also used in a sense safety toxicology as an important measure is well because at the end of the day, whether it's on target off target is what you we tend to want to find that out. So this occurs quite early with.

In our screening peer and so a rebuild the screaming tier of both at looking at looking at you know in a sense the effectiveness of the compound for selectivity and specificity. We also do a deep sequencing in our they see the monitor what else within the genome they may.

Unknown Executive: And so we build a screening tier both to look at, you know, in a sense, the effectiveness of the compounds for selectivity and specificity. We also do deep sequencing and RNA-seq to monitor what else within the genome they may hit. And we continue to try and improve not only the efficacy but the selectivity of that. We find that we're capable of doing that.

So we continue to try and improve not only the efficacy, but the select tivity of that we we find that we're capable of doing that as the molecules become a more effect. You know you tend to be into low nanomolar range. They tend to be far more selective of.

Unknown Executive: And as the molecules become more effective, you know, you tend to be in the low nanomolar range, they tend to be far more selective as a consequence of that. And then, obviously, we put them through the pharmaceutical, you know, not only for efficacy and safety but also for the pharmaceutical properties that go along with that. And, you know, that's a long laundry list of things that we look at, whether it's an induces SIP, whether it's AIMS assay issues, all the things that we look for that we know to look for that we, if we find some issue with it, we work it out and try and get that out until we get a compound that we want to move forward on to do what we'd say is to move forward, What we've talked about in the past for Huntington's disease is that we think that an orally bioavailable product, much like analogous to SMA, would really be the most competitive product.

With that and then obviously, we put them in through pharmaceuticals.

Not only do the efficacy and safety, but look at the pharmaceutical properties that go along with that.

You know that's a long laundry list of of things that we look at whether it's in induces sit within aims assay issues. All the things that we look you know that is known to look for that we if we find somebody issue with it we we work it out and try and get that out until finally, we get a compound.

Oh that we want to move forward dog food do what we'd say is to move forward like a development compound that we then do larger GMP scaling of the products. So we have that synthesizing the G.M.P. manner than both do GM GLP safety toxicology studies, what we've talked about.

Got it in the past four Huntingtons disease is that this we think that an orally bioavailable product much like analogous to estimate would really be the most competitive product and so there's a very important program for us where are we would anticipate if need be to continue to have as many compounds reported.

Unknown Executive: And so this is a very important program for us where we would anticipate, if need be, to continue to have as many compounds to move forward as we can. As I said in my prepared remarks, we already have a compound that we are doing GMP scaling and going to be moving into safety toxicology such that, as we've always said, we anticipate to have it in the clinic next year. So I think that's an exciting point here that we're moving forward on a compound and continuing, obviously, to build out the patent IP profile around all of that.

We can.

As I said in my prepared remarks, we already have.

A compound.

We are doing GMP scaling and good to be movie Didnt say to toxicology such that as we've always said, we anticipate that happened in the clinic.

Our next year. So I think that's an exciting point here that we're moving forward on a comp on continue obviously the build out the patent.

IP profile around all of that and then.

Unknown Executive: And then, you know, and we've already shown in animal models that it reduces HTT, not only in the brain but also in other tissues as well. And we'll have the advantage that we'll be able to look into the blood and see a reduction of that. These compounds are highly effective. We're shooting for probably a 60, between a 50 and 60 percent reduction. These molecules are effective enough to go pretty low, and so we're capable.

Already shown in animal models that have reduces.

HTP not only in the the brain, but also another tissues as well and we'll have the advantage that we'll be able to look into blog and see a a reduction of that these compounds are highly effective we're shooting for probably 60 between 50 and 60% reduction.

These molecules are effective enough to go pretty low.

And so were capable I think the nice thing about a small molecule also is that not only do we know it penetrate the blood brain barrier and gets into and obviously, it's because of the blood exposure gets the all fell within the brain, but you also gets into blog and skin and where it capable of actually monitoring with the effect.

Unknown Executive: I think the nice thing about a small molecule is that not only do we know it penetrates the blood-brain barrier and gets into, and obviously because of the blood exposure, gets to all cells within the brain, but it also gets into blood and skin. And we're capable of actually monitoring the effect of what exposure causes a reduction. And the fact that we could then go and figure that out to what effect reduction you see in the brain. So we have very good ways of titrating what the appropriate exposure is to get a 50, 60 percent reduction. And that's the way we pick the compounds and begin to define what would be the appropriate dose of that. And then we can go into humans, and really, as a consequence of being able to measure it in the blood, we're able to say what reduction we're able to see.

What exposure causes a reduction and the fact that is that we could then going to figure that out to what effect reduction do you feel right. So we've a very good ways of tight trading what the appropriate would be appropriate exposure is to get to a 50, 60% reduction and that's that's the way of that.

Where that's the way we pick the compounds and and begin to define what would be the appropriate dose of that and then we can go into humans and really as a consequence of being able to measure than the blood. We're able to say what reduction were able to see and I think one thing that we probably didn't push hard enough in the fund eight programs that very early on.

Unknown Executive: And I think one thing that we probably didn't push hard enough in the SMA program is that very early on in healthy volunteers, we were able to show that there was a reduction in SMA. Analogous to that, we're going to be able to show that the molecule that we chose will be able to say, you know, with the hypothesis, do you reduce HTT, and can you observe that in the blood? And we did that in SMA, and that gave us a lot of confidence to be able to move forward because what you see in the blood is what we saw in the brain. So that's, in a sense, one of the first. Even in healthy volunteers, I think we're going to have a good idea whether we hit the target we want, affect the splice, reduce the splicing, and then move on. And then, in terms of the product profile, I think we'll be sort of talking about that in more detail on the next call.

In healthy volunteers were able to show that there was a reduction of if I may analogous to that we're going to be able to show that the molecules. We chose we'll be able to say you know with the hypothesis do you reduce H T. T and can you observe that isn't the block and we did that in estimating that give us a lot of confidence to be up.

Well the move forward because what you see the blood is what we saw in the brain. So.

That's in the sense one of the first even in healthy volunteers I think we're gonna have a good idea whether we hit the target we won affect this blight reduced the spicy and then move on and then in terms of the product profile I think we'll be sort of talking about that.

In more detail over the next call.

Vincent Chen: Great. Thank you very much. I appreciate the insight. Thank you. Our next question comes from Joe Thome from Cowan & Company. Please go ahead. Hi there, congratulations on the quarter and thank you for taking my questions. Maybe the first one would be on the acquisition of the new products. I know you mentioned there are success-based milestones associated with the programs, but were there any upfront costs associated with the development of the programs? And then maybe a second on the dysautonomia program. I know you outlined the reasons as to why you're not moving forward with that, but is there any read-through to your oral splicing platform as a whole, and maybe how has this interaction changed your future development plans for rare diseases? Thank you.

Great. Thank you very much appreciate the insight.

Thank you. Our next question comes from Joe So me from Cowen and company. Please go ahead.

Hi, there congratulations on a quarter and thank you for taking my questions. Maybe a first one on the acquisition of the new products. I know you mentioned there was a success based milestones associated with the programs, but was there any upfront costs associated with the development.

And then maybe a second on the just on Nokia program I know you outlined the reason that's why you're not moving forward with that but.

Is there any read through to your Orals, placing platform as a whole and and maybe how is this interaction changed your future development plans for for rare diseases. Thank you sure I'll take the the sector. One person then I'll have Emily.

Joseph Patrick Schwartz: Sure. I'll take the second one first, and then I'll have Emily discuss the cost.

Discuss the costs I think I think this is an important point in.

Unknown Executive: I think this is an important point. Early on when we chose to look at FD, it was really a consequence of it being unique in that it had a founder's effect in terms of the mutation. It had a single point mutation that actually affected splicing in the L1 gene that prevented the production of the protein, and that led to disease. So it was very much a consequence of altered splicing.

Early on when we chose to look at F.D. It was really a consequence of it was unique in that it had a founders effect in terms of the mutation. It has a single point mutation that actually affect displacing the the up one gene that prevented the production of the protein and that lead to disease. So it was very much a contract.

With have altered splicing.

Unknown Executive: And just based on our understanding of it, we could fix it. But we knew that it was a relatively small patient population. But we thought it was strategically important to see if we could find another molecule, which I'm excited to say that we did, and it's highly effective. But it's a very small patient population, and we said to ourselves that, and it's a dwindling population. They now no longer have additional patients because they screened for this. And so we said that the best approach for such a small patient population would be a biomarker study. That is, we show that you reduce the level of the protein, and then, if possible, then go into a registry where you would follow it over time. We measured it as we did in the bars for about a year, but then we went on and did a post-marketing registry study.

And just based on our our understanding of where we could fix it but we knew that it was a relatively small a patient population.

But if we thought it was just strategically important to see if we could find another molecule, which I'm excited to say that we did and its highly effective.

But it's a very small patient population and we said to ourselves that.

And it's a dwindling population they now.

You know they now no longer have additional patients because they screened for that and so we said that the best we thought that the best approach for such a small patient population would be biomarker studies that it's every show that you've reduced the level of the protein and then if possible then to go into a registry where you.

I would follow it over time, we measures as we head into bars for about a year, but then go on into a commercial do.

Oppose marketing registry study.

And unfortunately, the F.D.A. wanted to have.

Unknown Executive: And unfortunately, the FDA wanted to have or suggested to us that we have a placebo-controlled study to perhaps look for other endpoints. And so in this case, and selected specifically for FDA, the small patient population, the fact that it would be placebo-controlled, we just didn't think there would be enough patients to be able to power and be able to do this. And the long-term two- or three-year study; we just didn't think it was viable, so that's why that stopped.

Suggested to us that we have a placebo controlled study on perhaps look for other endpoints and so in this case in selective specifically for empty. The small patient population. The fact that it would be placebo control, but we just didnt think there would be enough patients to be able to power and be able to.

To do this in the long term two or three years study. We just didn't think it was Bible. So that's why that stop in the case of other things. We don't think that's the case I mean, it huntingtons disease is much larger population.

Unknown Executive: In the case of other things, we don't think that's the case. I mean, Huntington's disease is a much larger population, and we think there's, you know, the good news is that there are others who are doing a substantial amount of work ahead of us, so they are helping to find what are the best endpoints, and what's the best way to power it. So we feel in a much better position in the case of Huntington's than, unfortunately, for HD. And I think that's relatively sad for the FD patients, and one of the causes we want to work on at the company is to try and think of a way where there's a – in a way like the Europeans have an exceptional circumstance that can allow for these extremely small patient populations to have a means to try and get approvals But that would obviously take time to change direction and laws for the company, but that's something I think we're going to try to work on in the long run.

We think there's you know to the you know the good news is that there's others, who are doing substantial amount of work ahead of us. So that are helping to find what are the best endpoints was the best way to the power. It. So we feel in a much better position in the case a huntingtons then unfortunately for HD and I think that's relatively sad for.

For the F b patients and one of the costs Oleds I think we want to work at the company is to.

Try and have it to try to think of away where there is a in a way in a way like the Europeans have an exceptional circumstances can allow for these extremely small patient population to have a means to try and get approvals on drugs that could be beneficial, but that would obviously take time, but the change direction.

Emily Luisa Hill: And then, in answer to your question about the upfront for the assets acquired from Bioelectron, we were pleased to have structured that as a success-based deal. The transaction has very little upfront payment, $10 million upfront for these assets, and then obviously, as Stu mentioned, their success-based milestones occur one year after certain regulatory approvals.

And loss for the comp, but that's something I think we're going to try to work on in the long run.

And then an answer to your question about the upfront for the assets acquired somebody Elektron lever pleased to structure that success.

The transaction has very little upfront payment 10 million upfront for these assets and then obviously as you mentioned their success based milestones to one year after certain regulatory approval.

Great. Thank you.

Joseph Patrick Schwartz: Great, thank you. Thank you.

Thank you.

Unknown Attendee: Our next question comes from Gina Wang from Barclays. Please go ahead. Hi, this is Peter from GNAT.

Our next question comes from Gena Wang from Barclays. Please go ahead.

Hi, This is Peter Fortinet I just had two quick questions Burstein SUNFISH part too could you give a sense of how what form that you would release the data would it be a press release, followed by medical conference in it so.

Marcio Sousa: I just had two quick questions. First, on Sunfish Part 2, could you give a sense of what format you would release the data? Would it be a press release followed by a medical conference? And if so, what kind of information would be included in the top line?

What kind of information would be put in a tough right now that quick follow up.

Unknown Attendee: May I have a quick follow-up?

Yeah.

Marcio Sousa: So, first, as you might recall, the trial is reading out in Q4, so we're trying to do this real-time, so it's going to be, the intent is for us, and we understand from Roche as well, to press release the top-line data. As it's practiced, both for us and Roche, the more complete results are going to be shown early next year at a conference, at a scientific conference, so we should be having this before the end of the year, the top line, and then next year, a more complete response.

Hey, Peter Marcia So so far as soon as you might recall rights that tries reading out in Q4. So we're trying to do this real time, so it's going to be things stance is for us and we understand ferocious while it's your press release that top line data as its practice a bowl for us and Roche.

The more.

Completes a results are going to be shown already next year and not conference in a scientific conference. So we should be having just before the end of the year to top line and then next year more complete response.

I've got it and I guess I guess my follow up question is.

Unknown Attendee: I've got it, and I guess my follow-up question is... Unknown Attendee

Given that I guess part to data would be available to before the approval decision would that be part of the discussion as well. Thank you.

Marcio Sousa: Yeah, absolutely. I believe we mentioned something to this regard on the previous call as well. While it's not required for the submission, as we made clear, it is courtesy, and it's obviously something we would be doing, and Roche, in this case, who are leading the submission, would be submitting that to the FDA, the top line data. What is not required here is to have a CSR format and all the data transfer and everything else that normally would be done, if it was a new submission. So the top line, again, as a matter of courtesy but also as a matter of practice, to be shown to the agency, presented to them if they have any questions, and so on.

Yeah, absolutely I believe we mentioned something to this regard than the previous call us while why it's not required for the submission.

Yes, as we made clear it is core to the any so obviously, we would be doing roche and escapes or leaving the submission with bits of meeting that to the FDA to top line data what is not required here is to have like a CSR format and other data transfer and everything else that's normally.

It would be if there was a new submission would be Dod so the topline a again as a matter of courtesy, but also as a matter of practice I should be shown to the agency presenter today and if they have any questions and someone.

Marcio Sousa: Obviously, very excited. I think the results of Part 1 and what we just showed at WMS and before that at many conferences show incredible activity for this compound and this patient in Type 2 and 3. So I'm looking forward to these results later in the quarter.

Obviously very excited I think the results on March one and what we just showed adopted a mass and before that that many confidence shows a incredible active at Ford This compounds and this patients in type two and three so looking forward should is results later in the quarter.

Great. Thank you very much.

Martin Halster: Great, thank you very much. Thank you. Our next question comes from Martin Halster from Credit Suisse. Please go ahead. Hey y'all, thanks for taking the questions. Had a couple. One was just from the press release you talked about, the RISD plan, NDA filing on the plan for the back half of the year. Just wanted to confirm, are we going?

You're welcome.

Thank you. Our next question comes from Martin Alister from Credit Suisse. Please go ahead.

Yeah. Thanks for taking the questions had a couple one was just from the press release you talked about the there is the planned NDA filing.

Unplanned for back half of the year just wanted to confirm or are we going to just pure about this filing once an FDA has accepted that and is that something we can expect by the end of the year and then the second question was just on the Friedreichs ataxia gene therapy I, Andy just wanted to see if you cut out a little more color to the process that kind of led to the.

Operator: https://www.fda.gov

Operator: And then the second question was just on the Friedrichs ataxia gene therapy IND. Just wanted to see if you could add a little more color to the process that kind of led to the slight push out from the end of this year towards the middle of next year and how confident you feel about the revised timeline. Thanks.

Like push out from kind of us here towards the middle of next year and how confident you feel about the revised timeline. Thanks.

Unknown Executive: Yes, sure. So I think there is a plan. I think we feel pretty confident that you're going to hear something by the end of the year. So we feel good about that. In terms of the F.A., I think, unlike A.D.C., it's a much larger population. We think about 25,000 patients.

Yes, sure. So I think the there is a privacy, we feel pretty confident that you're going to hear something by the end of the year.

We feel good about that in terms of the.

Okay I think unlike agency, it's a much larger population, we think about 25000 patients.

Unknown Executive: And what we did is we decided that we wanted to optimize the cell line a bit to get larger quantities produced. And so we decided to take the time to get that moving forward and to get that appropriately completed to be able to do that. And so our timelines now have moved, but we still think that, and what we're saying is, we still think that we will have I.M.D. Next year for F.A.

And we what we did as we decided.

That we wanted to optimize decelerated a bit to get larger quantities of producing so we decided to take the time to get that moving forward into got that appropriately completed owe it to be able to do that and so our timeline is now have moved but we still think that.

And what were what we're saying is we still think that we will have a indeed next year Oh for every day.

Unknown Executive: Okay, I'll just do one quick follow-up. On the Rooster Plan NDA, there will be an announcement when FDA has accepted the filing or when the filing has been submitted.

Okay steer one quick follow up on the rooms to plan and the a there'll be an announcement went after he has accepted the filing or when the filing its been submitted Oh accepted.

Martin Halster: Ah. Accepted

Okay, great. Thank you.

Brian Corey Abrahams: Okay, great. Thank you. Thank you. Our next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

Thank you.

Our next question comes from Brian Abrahams from RBC capital markets.

Unknown Executive: Hi, thank you very much for taking my questions. The first one is on risk deployment, SMA. As the SMA market and the data continue to evolve, what's been your latest feedback from regulators, physicians, and reimbursers as to the magnitude of benefit that would really resonate from Sunfish Part 2? And then separately, you mentioned that you're tracking on the AADC program towards your patient identification goal. Just wondering if you could give us a little bit more granularity around that, where the patients being identified are coming from geographically, through what channels you're finding them. And I'll hop back in the queue. Thanks.

Hi, Thank you very much for taking my questions.

First one on on risk to plan estimate.

He asked me market in the data continue to evolve what's been your latest feedback from regulators physicians.

And reimburse yours as to the magnitude of benefit.

That would really resonate from the SUNFISH part to that.

Lately, you mentioned that you're tracking on the AIDC program towards your patient identification call. Just wondering if you could give us a little bit more granularity around that.

Where are the patients being identified are coming from geographically to what channels that you're finding them and I'll hop back in the queue. Thanks.

Unknown Executive: Sure. So on the RISDA plan, I think, you know, people have seen the data that we presented in Part 1 of that, and I think they feel pretty good about that. We're looking at the results and, in a sense, the payment from the gene therapy program that seems to be getting paid for that. So we feel pretty good about where we're at. We think, obviously, not only do people like the efficacy and the fact that it's systemic and actually hits other tissues, which SMA does not – the lack of SMN affects, you know, like liver, bone, muscle, and other tissues as well, but the simplicity and the oral bioavailability of the drug, I think, is a real important factor. So we think the combination of the quality of the data that we've In terms of the second question, let me pass that over to Marcio.

Sure. So I'm the Arista plan I think you know people it seemed that data that we presented Oh from part one of them I think they feel pretty good about that we're looking at the results in a sense the payment from the from the gene therapy program that seems that they're getting paid for that so we feel pretty good about oh.

We're actually thing obviously, none of them people like the efficacy and the fact that systemic and actually fits other tissues.

And with estimate.

The lack of SMS effects, you know like liver bone muscle and other tissues as well, but the simplicity and the oral bioavailability of the drug I think as a real.

Important factors. So we think the combination of the quality of the data that we've shown thus far the ease of use is going to really put us in a very good and competitive position.

In terms of the second question, let me pets that over the Marcio sure Hey, Brian So the agency patient identification as I mentioned on the in the prepared remarks, we're making some good progress here towards our goal to have 300 patients available by the time of launch two cohorts venture reimbursements.

Unknown Executive: Sure. Hey, Brian.

Marcio Sousa: So the agency patient identification, as I mentioned in the prepared remarks, we're making some good progress here towards our goal to have 300 patients available at the time of launch to convert them to reimbursements. The main source of patients right now is twofold, right? One is our efforts at really connecting with families and physicians through social media, and that's been going quite nicely. And the second is our grass-roots approach in terms of visiting these physicians, understanding where the diagnosis is, and distributing kits. We had a very good number of kits distributed in the United States, where we are providing this at no cost, and outside as well.

The source of the main source of patients right. Now is twofold right. One is our efforts on recon actually families and physicians for social media and that's being panning out slight quite nicely in the second is our grass root approach in terms of visiting dispositions understanding.

Where the diagnosis and distributing kits, we had like a very good number off gets distributed in the United States, where we have provided does at no cost and outside as while you mentioned about geography.

Marcio Sousa: You mentioned geography in your question, so the key focus obviously is the U.S. That's the majority of our focus right now. That's where we expect to launch first, but we are putting some really nice efforts as well in some selected countries in Europe and in Brazil. So we have a relatively, I would say, restricted in terms of focus, geographic span for now, for the next 12 months. We're going to build success on success, so trying to get these patients in areas they're going to launch first. And the last source is identification through screening programs. So that's coming along. Now we have the sites open, as I mentioned, the previous quarter we had a little bit of a slowdown there, so that's now going to start to generate some patients. And then for next year, as we just mentioned, we expect to start newborn screening some patients in the United States. This is on top of the newborn screening program we announced last quarter that we're going to be having as a pilot in Germany. So it's all coming out quite nicely for a successful launch.

Question. So the key focus obviously is the last set that's the majority of our focus right now that's why we expect to launch farce, but we are putting some real nice effort. That's while in some selective counters in Europe and in Brazil. So we have a relatively I'll say restricted in terms of focus.

Geographic spend from four now for the next 12 months when a build success and success. So trying to get this patients on Arizona launch first and the last source is the identification through the screening problems. So that's coming along now we have the sites open as I mentioned the previous quarter here, we had a little bit up slowed down.

And there. So that's a now is going to start to generate some patience and then for next year.

As we just mentioned we expect to start newborn screening some patients Ingo. Neither states. This is all stop off the newborn screening problem, we announced last quarter, we're going to be having as a pilots in Germany. So it's all coming out quite nicely for successful launch.

Thanks, especially on Thanksgiving. Thank you express.

Brian Corey Abrahams: Thanks, Marcio, and thanks, too. Thank you. Thank you. Our next question comes from Raju Prasad from William Blair. Please go ahead. Thanks for taking the question, Kyu for me.

Thank you I'm next question comes from Roger Sachs from William Blair. Please go ahead.

Thanks, taking the question two for me.

Unknown Attendee: On MFASA, you mentioned the

And Plaza you mentioned the mix.

Marcio Sousa: So what would be the vision of Medicaid? Is that something that we should anticipate moving forward, and maybe just maybe some general color on how the label expansion is going so far for the product? And then on TechCity, it looks like in your 2023 projections, you have about $200 million for labor in TechCity. Can you just provide some color on how we should anticipate that launch to go and approximately what percent of that $200 million is earmarked for TechCity? Thanks.

So what utilization Medicaid is that something that we should anticipate moving forward and just maybe some general color on how the label expansion is going so far for the product and then on could study.

It looks like in your 2023 production by 200 million Clyburn Good study.

You just provide some color on or how we should anticipate that wants to go home and approximately what percent of that 200.

Okay. Thanks.

Sure. There is it's marcio here so first on a on the question and then on it flies right. So Medicaid we constantly when it's hard to use as you can imagine there's like new patients pretty much being added every day.

Marcio Sousa: Sure, this is Marcio here. So first on the question about influenza, right? So Medicaid, we constantly monitor its use. As you can imagine, there are new patients pretty much being added every day. We need to look into that on a rolling basis so we can meet our legal obligations with CMS and pay the rebates and so on quarterly. So when you look into that in the last few quarters, it was trending a little bit higher. In terms of the percent, we had to make some adjustments to make sure that we're okay in terms of gross to NATS. That results in a little bit of a negative impact on NATS revenue this quarter.

We need to look into that in a rolling basis. So he can meets our legal obligations with CMS and beta rebates and so one quarter does so when you look into that in the last few quarters. It was trending a little bit higher in terms of the percents than we expected to actually make some adjustments to make sure life.

Okay in terms of gross to nets that results in a little bit often negative impacts on the nats revenue this quarter when you're looking should that it's not only for the bass, but very importantly, our we revised our projections for the future based on the rate of patients are coming in and while the insurance plans are so we should be.

He is our best expectation right now that we should be cold hard fought the subsequent quarters in terms of the mix, we have and you're going up they do properly if not in terms of the label expansion.

Marcio Sousa: When you're looking at that, it's not only for the past, but, very importantly, we revise our projections for the future based on the rate of patients that are coming in and what the insurance plans are. So we're doing our field forces a lot, and our medical science liaisons, and our patient advocates are working a lot on getting the identification. Very nice early progress, but there is still a long road to go. So lastly, on TEC-SETI, I'm so excited, let me just say first, since your question is the first about TEC-SETI, the approval was officially published today, we received an advance note for MVISA that it would be coming, so the very first approval in the world for any to include quality of life in the indication statements.

The key here is not necessarily to converts to patients is that actually a relatively easy task is really this patients are not getting diagnose and they're not getting on on steroids. So we're doing our field force is working a lot in our medical.

Science liaisons on a patient advocates are watching a lot on gotten densification very nice early progress, but it is to alone roads juggle.

Lastly on the tax Saturday so extremely excited let me just say that first since you are questions. The first about big Sadie.

Officially publish the approval today, we've received that advance notice from visa that it would be coming so the very first approval in the award for any to include quite a fly into indication I statements.

Marcio Sousa: So as we talk about differentiation, competitive markets, we wanted to make sure we're always ahead of everyone, so that's very nice. When you look at our long-term projections, Brazil is the most important market in the region, with about 5,000 patients. It puts us ahead in terms of negotiations with the government, and that's where we're gonna start now, but very importantly, while we've been preparing the market, and we have a decent number of prescriptions already, we couldn't promote, we couldn't say the word TEC-SETI, we couldn't talk about the label. So as of tomorrow, the team in Brazil is gonna be talking about this to physicians, so we The first year is normally slow in terms of revenues, but we are obviously going to do our best, and more than that, even deliver on results, but I would try, if I were modeling, if I were in your shoes, I would have put a little bit of a slower first 12 months and then ramping up from there.

So as we talk about differentiation a competitive markets. We want that you make sure. We're always ahead of revenue won so that's very nice when you look into our long term projections, Brazil was the most important markets in the region about 5000 patients. He puts US ahead in terms of negotiations with the government and that's what I'm going to starts now.

Very importantly.

Why would be preparing to markets and we have a defense number of prescriptions for already couldn't promos. We couldn't say the award that fatty we could then talk about the label so as off tomorrow. The team in Brazil is gonna be talking about this June physician, so going to be seeing hopefully a very nice increasing demand and what's going on parts to revenues the first years.

It is low.

In terms of revenues, but we do obviously going to do our best in more than that event you should that even on results, but oh, let's try if I were modeling I was in your shoes I would be putting a little bit Delphi is lower first 12 months and then ramping up from that.

And one small just point to the 200 million for Tech savvy was really I think what we put for ticks every year we wish.

Unknown Executive: One small point was the $200 million for TXETI was really, I think, what we put into TXETI and we left. We had about $150 million for TXETI, so it was the majority of the money.

We had about $150 million for.

So that's right.

Great. Thanks.

Unknown Attendee: Great, thanks. Thank you. Thank you. Our next question comes from Joel Beattie from Citi. Please go ahead. Hi, thanks for taking the questions. The first one is, could you discuss the importance of showing a statistically significant benefit in Sunfish Part 2 compared to placebo from both a regulatory standpoint as well as from a commercial success standpoint? And then the second question is, you know, could you discuss the confidence in DMD revenue guidance for the year? It implies an uptick from where it was this quarter, you know, and, you know, any thoughts on whether it could be towards the bottom or the upper end of the range?

Thank you.

Thank you.

Our next question comes from Joel Beatty from Citi. Please go ahead.

Hi, Thanks for taking the questions. The first one is <unk> could you just because the importance of showing a statistically significant benefit and SUNFISH part two compared to placebo from both the regulatory standpoint, as well as commercial success standpoint, and then the second question.

Could you discuss.

The confidence and DMD revenue guidance for the year it implies a uptick I'm from where it looks at this quarter.

Yeah, and any thoughts on much but he could be towards the bottom or the upper under the range.

Yeah.

Sure. So on the if at some fish part your rights and why do we expect from that trial, obviously extremely bullish in terms off the problem in general and this is based on what it look in two parts one or so the way the try what spa words as it relate.

Joel Beattie: Sure, so on Sunfish Part 2, right, and what we expect from that trial, obviously extremely bullish in terms of the program in general, and this is based on what we looked at in Part 1. So the way the trial was powered is in relation to, obviously, it's always a ratio between the point estimate change and the standard deviation. So in this case, we expect it to be three points change on the MFM32, that is the primary endpoint, and a six standard deviation for that.

Since you obviously, it's always a ratio between the point estimate change than they standard deviation on this case, we expect it should be a three points changed on the MSM 30 Chew that is the primary endpoint in the six a standard deviation Ford. That's this is pretty much what it was seen with part one so and Thats really.

Marcio Sousa: This is pretty much what we've seen with Part 1. So in that regard, there are all indicators that the trial is going in the right direction. The good thing is that this population should be more homogeneous, so one would expect that the results are a bit more homogeneous as well.

Cards like that is all indicators that tries going there either action. The good thing is this population should be moral more genius. So one would expect that the results are a bit more imaging is us well.

Marcio Sousa: It is important to have a positive trial, and obviously that's what we are planning for, right, both for the regulators, payers, patients, and so on. But it's very hard for us to try to predict right now where it's going to land. This trial was well conducted, extremely well conducted, more than 186 patients, or sorry, 168 patients, always inverse the two numbers there, my apologies, and powered properly. So all we could do to the risk was done, and again, we're excited to hear about that before the end of the year and inform you guys. In terms of the DMG guidance for the year, it is trending positively, you're absolutely right. We continue to, just like our approach to guidance, as we always say, is to be realistic in terms of what can be achieved at this point in time because we do have some ordering pattern issues. We didn't feel it was the right thing to narrow the guidance. We're obviously excited, we're going to do our best, and we're all pushing here to be as high as possible, but the most responsible thing for us was to keep the entire range of the guidance open. Thank you.

It is importance.

You have a positive trial and obviously that's why we are planning for by both for the regulators Bay or spacious and still want it's very hard for us to try to predict right now what it was gonna lands described was well conducted extremely well conducted a mark 186 patients are sorry 168 patients.

Always seems arts that your numbers that my apologies.

And power properly. So all we could do to de risk was Don and again, we're excited to hear about that before the other fee, earning farm you guys in terms of the GMV guidance for the year. It is trending positively you're absolutely right.

We continue to just like a lot approach for guidance as we always say it should be realistic in terms off what can be achieved at this point in time, because we do have some ordering patterns fluctuation. We didn't feel was the right thing should narrow the guidance.

Obviously excited I'm going to do our Bath and we are pushing here to be as high as possible, but the most responsible thing for us while still keeping our range if the guidance open.

Great. Thank you. Thank you.

Thank you.

Joel Beattie: Our last question comes from Eric Joseph from J.P. Morgan. Please go ahead. Hey, good evening. This is Turner on behalf of Eric. Just to follow up on Huntington's and in thinking about entering the clinic with healthy volunteers next year and getting some initial PD data, do you have a sense yet of what level of plasma mRNA and HTT protein reduction would give you some confidence to meet the 50 or 60% reduction threshold in the CNS that would confer some efficacy? And then one other quick one. I'm just curious as to when we may anticipate updates for jewelfish and rainbowfish and any particular recruitment update for rainbowfish. Thank you.

Last question comes from Eric Joseph from Jpmorgan. Please go ahead.

Hey, good evening. This is turnaround for Eric just a follow up on Huntington and thinking about entering the clinic with healthy volunteers next year and getting some initial PD data do you have a sense yet of what level of plasma and Marni and GP protein reduction would give you some confidence to meet the 56 50 or 60% read.

Option threshold in the CNS that would conversant efficacy and then one another quick one im just curious as to when we may anticipate updates for dual fish and Rainbow fish and any particular recruitment update for being bullish. Thank you.

Sure.

Unknown Executive: Sure. In the case of HTT, we probably, you know, obviously we're looking to see some change in that. You know, obviously, what we're shooting for is somewhere between 30% and 60% reduction of the HTT protein, so that's what we would consider important. So we think that within the blood and brain, the blood-brain barrier, that there's a good, almost a one-to-one ratio between the exposure that you see in the blood and what you see in the brain. So we'd be pretty confident that the results that we get from the And again, I think the importance of that is that, obviously, you know, because it's in the blood, it would get distributed to all cells within the brain. And, you know, actually, I think that's actually an important point because, you know, there are certainly deep recesses in the brain that are difficult to get to, and we think having the exposure in the blood really gives us a big advantage.

In the case of 82, Yeah, we probably no obviously, we're looking to see some.

Some change of that obviously, what we're shooting for somewhere between 30 and 60%.

Reduction of the H T P protein so thats, what we would consider.

Important so we think.

That we know that within the blood and bring the blood brain barrier that there's a a good almost a one to one ratio within the exposure that you see in blood is what you see in the brain, so we'd be pretty confident that.

The results that we get from plug would be indicative of what you're seeing in the brain and again I think the importance of that is that obviously.

The.

Because it's in blood it would get distributed to also all cells within the brain and you know X. I think that's that's actually an important point because if you know there are.

Certainly be recesses of little blip in the brain that are difficult to get to rethink by having the exposure in the blood really gives us some big advantage.

And maybe I can take the second on the other trials for us. It may so rainbow efficient, it's probably get that one where the most excited to see snacks right. So you probably see our update adopted a mass dosed. The first patients there are having really great interest several sites up and globally.

Marcio Sousa: And maybe I can take the second on the other trials for SMA. So, Rainbow Fish is probably the one we're most excited to see next, right? You probably see our updates at WMS. Those, the first patients there, are having really great interest; several sites are open globally. That should, as it comes, we're going to be showing updates. I think it's being practiced for this program to be present at all the major scientific conferences. There are obvious ones at the beginning of the year, like AN, and that's where you should expect to have a general update for the program.

That should as it comes from going to be showing updates I think as being practice opt for this program to be presence in all the major scientific conference that obvious ones at the beginning of the year like and and Thats why we should expect to have a general update for the problem.

Great. Thank you.

Marcio Sousa: Great, thank you. Thank you. Thank you. This concludes our Q&A session. At this time, I'd like to turn the call over to Stuart Pelt, CEO, for closing remarks. Please go ahead, sir.

Thank you.

Thank you. This concludes our given a session at this time I'd like to turn the call over to Stuart Peltz CEO for closing remarks. Please go ahead Sir.

Unknown Executive: Well, again, let me just thank you all for joining the call today. We really appreciate it. And I think what you've seen thus far is that we've really had a productive year thus far with a number of exciting milestones that will be coming, I think, in the coming weeks. And we look forward to sharing those with you. Again, thanks for being a part of our call.

Well again, let me just thank you all for joining me.

The call today, we really appreciate it and I think what you could see thus far that we've really had a productive year, thus far with a number of exciting milestones that will be coming I think in the coming weeks and we look forward to sharing those with you.

Again, thanks for being a part of our call.

Ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect good day.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Good day. Thank you for watching!