Q1 2022 PTC Therapeutics Inc Earnings Call

Operator: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Once again, ladies and gentlemen, please stay on the line. [music] BF-WATCH TV 2021 Ladies and gentlemen, thank you for standing by and welcome to the TTC First Quarter 2020 Financial Call. At this time, all participants are in a listen-only mode.

Ladies and gentlemen, please standby your conference call will begin momentarily once again, ladies and gentlemen, please stay on the line.

[music].

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to turn the call over to your host, Kylie O'Keefe. Good afternoon, and thank you for joining us today to discuss the PTC Therapeutics First Quarter 2022 Corporate Update and Financial Results. I am joined today by our Chief Executive Officer, Stuart Pauwels, our Chief Operating Officer, Matthew Klein, our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Emily Hill.

Ladies and gentlemen, thank you for standing by the Ptc's first quarter 'twenty.

At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session.

During the special need to press Star one on your telephone if you require any further assistance. Please press star Zero I would now like to turn the call over to your host Keith you begin.

Good afternoon, and thank you for joining us today to discuss the PTC therapeutics first quarter.

2020, a corporate update and financial results.

I'm joined today by our Chief Executive Officer Talbott our.

Our Chief operating Officer, Matthew Obrien, our Chief Business Officer, Eric Powell, and our Chief Financial Officer Emily Hill.

Kylie O'Keefe: Today's call will include forward-looking statements based on current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements. Our action results materially differ from a poll-voting statement.

Today's call will include forward looking statements based on current expectations.

Please take a moment to review the slides posted on our Investor Relations website.

Junction with the coal which contains our forward looking statements.

Our actual results could materially differ from the forward looking statements.

Kylie O'Keefe: As such, these forward-looking statements are subject to risks that 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 annual report on Form 10-K and quarterly reports on Form 10-Q 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, non-GAAP financial measures, and a reconciliation of GAAP to non-GAAP financial measures is available in today's earnings release. With that, let me pass the call over to our CEO, Stuart Seuss. Thanks for having me.

Statements are subject to risks that can materially and adversely affect our business.

And results of operation.

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

<unk> filings.

We will displace that non-GAAP information during this call information regarding our use of GAAP and non-GAAP financial measures and a reconciliation of GAAP non-GAAP is available in today's earnings release.

With that let me practical either Tibet.

Okay.

Thanks, Charlie.

Stuart Pauwels: Good afternoon, and thanks for joining today. I'm excited to share PTC's first quarter results, the first update in what I expect to be a transformative year for the company. Our mission at PTC is to develop therapeutics to help treat patients with rare disorders while producing revenue to provide value for all of our patients.

Good afternoon, and thank you for joining today I'm excited to hear Ptc's first quarter results. The first update what I expect to be a transformative year for the company.

Our mission at <unk>.

Develop therapeutics to help treat patients with rare disorders, well producing revenue right value for all of our stakeholders.

When I founded the company. It was built on the ground breaking science foreign they play out.

Stuart Pauwels: It was built on the groundbreaking science of RNA biology. By regulating at the RNA lab, we discovered the three diseases of iron pentachromia. The company has worked hard to turn these ideas into reality. Over the past 24 years, we have grown into an enduring biopharmaceutical company with a number of commercial products. We are continuing to build a robust pipeline of advanced new therapeutics that, at a steady pace, will deliver a new product every two to three years.

By regulation at the RNA level.

We realized good treatment.

Pieces of iron.

The company has worked hard to turn things back to you.

Give them a reality.

Over the past 24 years, we have grown into an enduring biopharmaceutical company with a number of virtual products.

We are continuing to build a robust pipeline of new therapeutics.

<unk> will deliver a new product.

Through the three year.

Stuart Pauwels: This will allow us to continue to build into a company with substantial revenue that brings growing value to all of our stakeholders. Let me start with our commercial portfolio. I'm proud to report that our net product revenue for the first quarter was $130 million, which represents 42% growth over the first quarter of 2021.

This will allow us to continue to build into a company with a substantial revenue that Britain.

Growing value for all of our stakeholders.

Let me start with our commercial portfolio.

Good to report that the <unk>.

Net product revenue for the first quarter was $130 million, which represents 42% growth over the first quarter of funding funding one.

Stuart Pauwels: Our Duchenne Muscular Dystrophy Franchise Net Product Revenue was $128,000,000, demonstrating another strong quarter for Transbarna and Inspire. In addition, we recently had the first group purchase order for TECFEDI in Brazil, which will be recognized in the second quarter. Eric will go into more detail on our substantial commercial progress later in the call. RISD sales continue to show strong growth in all regions with substantial growth in Europe. RISD continues to be the most prescribed disease-modifying therapy for SMA with more than 20% market share in the United States and more than 30% market share in Germany.

We shed muscular dystrophy franchise net product revenue was $128 million demonstrating another strong quarter for embargo and Bob.

In addition, we recently had first group disorder protect Saturday in Brazil, which will be recognized in the second quarter.

Ill go into more detail on our substantial commercial progress later in the call.

Ah repeat sales.

<unk> showed strong growth in all regions with substantial growth in Europe .

<unk> continues to be the most prescribed disease modifying therapy for SMA with more than 20% market share in the United States and more than 30% market share in Germany.

Stuart Pauwels: It is currently approved in 79 countries, and we're excited about the continued rapid uptake and the sustained growth of EBRSTI, which demonstrates the demand across all FMA patients for an effective, poorly-administered therapy. We have several exciting near-term value drivers that I'd like now to provide some updates on. For our first gene therapy for AAGC deficiency, we recently announced that we have completed the Scientific Advisory Group and Oral Explanation Meetings with the Committee for Advanced Therapy, or CAD. With the successful completion of these meetings, we now expect a cease and desist opinion in May.

It is currently approved in 79 countries.

Talking about the continued rapid uptake.

<unk> growth.

Which demonstrates that the bands across all that for many patients.

Orally administered therapeutics.

We have several exciting near term value drivers.

I'd like now to provide some updates on.

For our first gene therapy for ADC deficiency, we recently announced that we've completed the scientific advisory group and the oral explanation meetings with the committee before it became clear.

Yes.

With the successful completion of these meetings.

We now expect to see some.

The opinion in May.

Stuart Pauwels: If approved, PTC AADC would be the first targeted gene therapy administered directly into the brain. We're very proud to have gotten to this point in the European regulatory process, and we'll now focus efforts on submission of the BLM. Turning now to development, where we have five ongoing registration-directed trials. The first of these is Study 041, the placebo-controlled trial of translinase.

Through PTC a D C would be the first mark.

Therapy administered directly into the brain.

We're very proud to have gotten to this point.

The European regulatory process and will now focus efforts on submission of the BLA.

Turning now to development programs, where we have five ongoing registration directed trial so.

The first of these is steady at four one.

Controlled trial of screens Barnes.

Stuart Pauwels: We expect to report the results of Study 041 by the end of the second quarter. We have also recently received a positive CHMP opinion for the eighth annual renewal of translinase in the EU. Turning now to PTC 923 for PKU and the Registration-Directed Affinity Study, we're excited by the opportunity in PKU, with a well-established patient population and a high amount of medical needs driven by the majority of PKU patients, either therapy naive or partly controlled on existing therapy.

Back to report results of <unk>.

Study O 41 by the end of the second quarter. We also recently received a positive <unk> opinion.

Opinions for the eighth annual renewal and find out in the EU.

Turning now to <unk>.

Two nine.

Q and the registration directed study.

We're excited by the opportunity.

With the well established.

And a high unmet medical need driven by the majority of PKU patients.

Beer P naive are poorly controlled on existing there.

Stuart Pauwels: In addition, the AFFINITY study has an enriched population, a biomarker endpoint, and a defined path through registration. Results are expected from this study by the end of the year. For the BioE, we expect results from the Registration-Directed MI-DE Study of Ataquanone in Patients with Mitochondrial Disease-Associated Seizures in the fourth quarter of this year. We are also excited to announce that we initiated a Cardinal ALS study in DGC 857 in ALS, moving to our validated site. We're excited to be following the successful pathway established by EBRSDI with PTC518 in Huntington's Disease, or HD. HD is a debilitating disease with no disease-modifying treatment.

In addition, we have.

These studies have been enriched population, a biomarker endpoint and a defined path to registration.

Both are expected from this study by the end of the year.

For the bio E platform.

We expect results from the registration directed <unk> study a particular node.

For mitochondrial disease associated feature in the fourth quarter of this year.

Where are we are also excited to announce that we initiated a.

Got it and DTC eight five.

A L S.

Moving to our validated.

Platform, we're excited to be following the successful path right.

Stablish Rusedski.

With PTC by Wednesday, and Huntington's disease or HD.

HP is a debilitating disease with no disease modifying treatment.

Stuart Pauwels: For PTC 508, an oral splicing modifier, we initiated the Phase II Pivot HD study in patients with Huntington's disease in the first quarter of this year, and we look forward to data from the first 12 weeks by the end of the year. We have also recently initiated the SUNRISE LMS study of Unethelin and Leomyosarcoma. We are excited to make progress with this platform and will provide additional updates in the next quarter.

For PTC 518, and oral splicing modifier.

David.

Phase II pivotal <unk> study in patients with Huntington's disease in the first quarter of this year and we look forward to data from the first 12 weeks by the end of the year.

From a policy portfolio.

We also recently initiated the Sunrise LMS study of ethical and legal miles sarcoma.

We're excited to make progress with this platform and we will provide additional updates in the next quarter.

Stuart Pauwels: I'm proud that while PTC has demonstrated success with RNA science, we have worked to grow and diversify the business to increase the strength of the pipeline for continued success that will result in multiple therapies over the next decade. I'll now turn the call over to Matt for more detail on clinical development.

I'm proud that PTC has demonstrated that with R&D side, we have worked to grow and diversify the business.

The strength of the pipeline for continued success.

Produce multiple therapies over the next day.

Now the call over to Matt for more detail on clinical develop.

Matt.

Matthew Klein: Thanks to you, our development teams continue to work hard to progress all of our pipeline programs. We have a number of ongoing registration-directed trials that we expect to read out this year, and several additional studies being initiated. I'll begin with our Affinity Phase III trial of PTC 923 in patients with PKU. Enrollment in the Registration-Directed Affinity Trial is ongoing, and we expect to have results by the end of 2022. As a reminder, the AFFINITY trial is a six-week placebo-controlled study with a primary endpoint of reduction in blood phyloionine.

Okay.

Well continue to work hard progressing all of our pipeline programs.

A number of ongoing registration directed trials expected to read out this year and several additional studies.

Matthew Klein: To enrich the randomized study population for likely PTC923 responders, the study includes a run-in phase during which potential subjects are treated with PTC923 for two weeks. Subject to demonstrated response to treatment, a 15% reduction in phenylalanine levels will continue the placebo-controlled treatment.

I'll begin with our phase III trial of PTC 93 in patients with PKU.

<unk> and our registration directed unity trial is ongoing and we expect results by the end of 2022.

As a reminder, the affinity trial the six week placebo controlled study with a primary endpoint of reduction in blood phenylalanine.

To enrich the randomized study population for likely PTC 93 responders. This study includes a running phase during which potential subjects are treated with PTC 90 threes in two weeks.

Subject to demonstrate a response to treatment.

15% reduction in panel alanine levels will continue.

Controlled.

Matthew Klein: Following completion of the Ego Control Study, all subjects will be eligible to enroll in a long-term extension. Next, I'll discuss our BioE file, from which we currently have two ongoing registration-directed trials, in particular, and an additional registration-directed trial with PTC 857. The MIGHTY trial, the Registration Directed Trial of Adiquinone in Patients with Mitochondrial Disease Associated Kinesias, is actively enrolling patients, and we expect results by the end of 2022. As a reminder, this study will enroll approximately 60 patients from study sites worldwide. This study includes a four-week run-in phase to ensure patients are having a minimum number of observable motor seizures, followed by a 24-week placebo-controlled phase during which subjects will receive either a placebo or a betafluenza vaccine.

Following completion of.

Placebo controlled study all subjects will be eligible to enroll in a long term extension study.

Matthew Klein: The study's primary endpoint is reduction in the number of observable motor seizures, with secondary endpoints capturing other aspects of disease morbidity. The second particular non-registration-directed trial is the Phase 3 MOVE-FA study in patients with rejected taxes. The trial includes a 72-week placebo control phase, and the primary endpoint is changed from baseline on a modified freezer catastrophe rating scale. This global study is fully enrolled, and we expect results in the second quarter of 2023. Turning to the second compound in the BioE platform, PDC857, we have now initiated a Phase 2 registration-directed cardinal study in amyotrophic lateral sclerosis.

Next I'll discuss our bio repo.

On which we currently have two ongoing registration directed trials, particularly.

An additional registration directed trial with PTC.

The <unk> trial registration directed trial in particular down in patients with mitochondrial disease associated seizures is actively enrolling and we expect results by the end of 2022.

As a reminder, this study will enroll approximately 60 patients from 70 sites worldwide.

The study includes four week running.

To ensure patients are having a minimum number of observable motor seizure.

All led by a 24 week placebo controlled phase during which subjects will receive either placebo or <unk>.

The study's primary endpoint is reduction in the number of observable motor seizure with secondary endpoints, capturing other aspects of disease.

The second, particularly non registration directed trial the phase III move at pace.

In patients with <unk> ataxia.

The trial includes a 72 week placebo control and the primary endpoint is changed from baseline in the modified we hit the taxpayer ratings scale for him.

This global study fully enrolled and we expect results in the second quarter of 2023.

Turning to the second compound from <unk> from PTC advisors, Kevin We have now initiated phase II registration directed Cardinal study and amyotrophic lateral sclerosis patients.

Matthew Klein: This trial includes a two-month screening phase to establish a baseline rate for disease progression, followed by a 24-week placebo control phase, during which subjects will receive PCC 857 or placebo. The study is planned to enroll approximately 255 patients from study sites worldwide, and the primary endpoint is the change in ALS-FRS score from baseline to 24. Turning now to our, We recently announced the initiation of the Phase II PIVOT-HT study of PTC518 in Huntington's disease patients. As a reminder, the PIVOT HD7 consists of two parts.

This trial includes a two month screening phase to establish a baseline rate of disease progression.

Followed by a 24 week placebo controlled phase during which subjects will receive PTC 85, seven or placebo.

The study is planned to enroll approximately 265 patients from study sites worldwide and the primary endpoint is change in ALS FRS score from baseline to 24 weeks.

Turning now to our HIFU platforms, we recently announced the initiation of the phase III pivotal HD spin of PTC, <unk> and Huntington's disease patients.

As a reminder, the pivotal <unk> study.

Sure.

Matthew Klein: The first part is a 12-week placebo-controlled phase focusing on safety, pharmacology, and pharmacogenetic effects on Huntington's mRNA and protein. After completing the first 12 weeks, all subjects will remain on their initial treatment assignment of either PTC 518 or placebo for an additional nine months, during which we will apply FLUDD, CSF, and radiographic biomarkers. This study will initially include two dose levels, 5mg and 10mg. The answer is B, dear.

The first part of the 12 week placebo control focusing on safety pharmacology and pharmacokinetics okay.

Mrna and protein.

After completing the first well all subjects will remain on their initial treatment assignment of either <unk> or placebo for an additional nine months.

<unk>, which we looks like flood CSS and radio graphic biomarker data.

Study will initially include two dose level five milligrams and 10.

Matthew Klein: I think that's all we've studied for the end. I will now turn to our apology and the recently-initiated SUNRISE LMS study, which is the registration-directed phase 3 study of UNESCO in patients with leiomyocarcoma. Leiomyocarcoma, or LMS, is a rare and aggressive cancer found in blue muscle. It is also one of the most aggressive sarcoma subtypes and has a high risk for recurrence, leading to a poor clinical prognosis. Several chemotherapeutic regimens are utilized for elastorefractory health.

We anticipate data from the 12 week study by the end of this year.

I will now turn pharmacology platform and our recently initiated Sunrise LMS study, which is the registration directed.

Okay.

In patients with Leiomyosarcoma.

<unk> sarcoma Farhan, Matt is a rare and aggressive cancer.

Okay.

Also one of the most aggressive sarcoma subtypes and has a high risk of recurrence meaningful poor prognosis.

Several chemotherapeutic regimen are utilized for <unk>.

The refractory ounces.

Matthew Klein: But with an objective response rate of only 7-9%, they offer minimal, meaningful outcomes. Sunrise LMS is a global placebo-controlled study enrolling patients with relapsed and refractory LMS. Target enrollment is approximately 345 patients, and the primary end point is progression-free survival. The SUNRISE LMS study is based on the findings from our Phase 1b trial, in which insulin was found to be well-tolerated and demonstrated a treatment effect in patients with relapsed prefractory LMS who had previously completed 3, 4, or 5 Lyme. In summary, I am proud of our continued progress across the pipeline and look forward to providing updates I will now turn the call over to Eric for an update on our commercial progress. Thanks, Pat.

And objective response rate of only 79% a offer minimal meaningful efficacy.

Sunrise LMS is a global people controlled study enrolling patients with relapsed refractory element.

Target enrollment is approximately 345 patients and the primary endpoint is progression free survival.

The Sunrise element studies based on the findings from our phase <unk> trial, and wishing Epsilon was found to be well tolerated and demonstrated a treatment effect in patients with relapsed refractory <unk> that we had previously completed three four or five lines of therapy.

In summary, I am proud of our continued progress across pipe.

And look forward to providing updates on our programs over the course of the year.

I'll now turn the call over to Erik for an update on our commercial progress.

Eric.

Thanks, Pat the.

Eric Pauwels: The commercial team kicked off the year with a very strong quarter, building on the momentum that we created last year. So far, 2022 is shaping up to be a transformative year for PTC and, in particular, for the customer-facing team, with potential launches in Europe and other international markets for PTC AADC and, in Brazil, Special Approval for the New Indication, or Way Lever, for Familial Partial Lipodyst David Lebowitz [inaudible] We continue the expansion of our geographical footprint in Transilvania.

The commercial team has kicked off here with a very strong quarter building on the momentum that we created last year. So.

So far 2022 is shaping up to be a transformative year for PTC.

And in particular for the customer faced with potential launches in Europe , and other international market for PTC agency and in Brazil.

Central approval for the new indication of why Libre.

For familial partial lipodystrophy or yes.

In addition.

We continue the expansion of our geographical footprint for Translarna.

Eric Pauwels: Our Global D&D Franchise continues to deliver robust revenues across all regions. For example, our first quarter revenue for the DMV franchise was $128 million, which is an impressive 42% growth over the first quarter of last year. Let me start with applause. Our Implaza Net Product Revenue for the first quarter was $49 million, double-digit growth from the first quarter of last year. Ongoing execution by our employee team drove new patient starts, more favorable access, continued high compliance, and appropriate wait-based dosing. Now, turning to Trayvon.

Our global DMD franchise continues to deliver robust revenues across all regions.

Our first quarter revenue for the DMD franchise was $128 million.

Which is an impressive 42% growth over the first quarter of last year.

Let me start with implant them.

Our implied net product revenue for the first quarter was $49 million.

Double digit growth from the first quarter of last year.

Ongoing execution by our employee team drove new patient starts more favorable access.

Hi, compliance and appropriate weight based dosing.

Now turning to transpire.

Eric Pauwels: We achieved $79 million in net product revenue for the first quarter. TransLara continues to be robust and globally diversified with growth in long-standing existing markets and new geographical markets. Year-over-year growth was predominantly driven by Brazil, where we completed delivery on the remainder of the Ministry of Health group purchase order that we had partially delivered in the fourth quarter of last year. We are continuing to expand our presence in markets in Asia-Pacific as these markets have the potential for continued growth of the brand in the future. Now, moving on to our progress with Head Study and Reliever. Our Latin American team continues to build significant momentum in the region.

We achieved $79 million and.

Net product revenue for the first quarter.

So in Florida continues to be robust and globally diversified with growth and long standing existing markets and new geographical markets.

Year over year growth was predominantly driven by Brazil.

We completed delivery on the remainder of the Ministry of Health Group purchase order that we had partially delivered in the fourth quarter of last year.

We are continuing to expand our presence in markets in Asia Pacific as these markets have the potential for continued growth of the brand in the future.

Now moving onto our progress will take steady and way Libra.

Our Latin American team continues to build significant momentum in the region.

Eric Pauwels: As Stu mentioned, in Brazil, following the Innovative Drug Classification Cortex Study, we are excited to have received the first group purchase order from the Ministry of Health, which will be recognized in the second quarter. Now this is a significant milestone that reflects the growing number of HATTR patients in Brazil awaiting treatment. Furthermore, patient identification continues to be strong, and we anticipate additional group work disorders over the course of the year. Finally, the team has submitted the HPA dose paper, Tech Study, to ComiTech, which is the National Commission for the Incorporation of Technologies, and has initiated discussions for inclusion of Tech Study in the essential drug list, which simplifies long-term access.

As Sue mentioned in Brazil, following the innovative drug classification protect study. We are excited to have received the first group purchase order from the Ministry of health, which will be recognized in the second quarter.

Now this is a significant milestone which reflects the growing number of <unk> patients in Brazil are waiting.

Furthermore, patient identification continues to be strong and anticipate additional purchase orders over the course of the year.

Fine.

Team has submitted the HCA does take protect study <unk>, which is the National Commission for the incorporation of technology and has initiated discussions for inclusion of Tech study and the essential drug list, which simplifies long term asset.

Eric Pauwels: We continue to build our presence in Latin America with ongoing regulatory submissions for TRANSLARDA, TED-STUDY, and a recent first quarter NDA submission for WeLever in Mexico, making this our third innovative product to be submitted in this time period. As a reminder, last December, we submitted an application to NVPEN Brazil for approval of weight lever for the treatment of FCL. If approved, Waylieber will be the first approved treatment for FDL in Brazil, and this will mark the first approval globally for this medication.

We continue to build our presence in Latin America with ongoing regulatory submissions of trends, Florida Chegg study at the recent first quarter NDA submission we lever it.

Making this our third innovative product you submitted in this country.

As a reminder, last December we submitted an application to <unk> in Brazil.

The approval of way labor for the treatment of FPL.

If approved.

We lever will be the first approved treatment for FPL in Brazil.

And this will mark the first approval globally for this indication.

Eric Pauwels: We anticipate a decision in the second half of 2022. Now, I will touch on preparation for PTC's first gene therapy launch for AADC deficiency. We are very excited about the forthcoming CHMC opinion in May, and our team is ready to execute on the launch of the AADC gene therapy in Europe shortly after potential approval. Expert neurological centers of excellence in key European countries have been identified, qualified, and are ready to treat patients post-approval.

We anticipate a decision in the second half of 2022.

I will now touch on the preparation for Pcs first gene therapy launched four ADC deficiency.

We are very excited about the forthcoming <unk>.

Opinion in May.

And our team is ready to execute on the launch of the ADC gene therapy in Europe shortly after potential approval.

Expert neurological centers of excellence in key European countries have been identified.

Qualified and are ready to treat patients post approval. Many of these centers are also being prepared to treat ADC deficiency patients via early access programs in the near future.

Eric Pauwels: Many of these centers are also being prepared to treat AADC deficiency patients via early access programs in the near future. Identification and preparation of additional centers globally are on track, and PTC's efforts to accelerate patient screening and identification activities in enriched, high-risk populations continue to progress well. In conclusion, the commercial team is off to a strong start and has set the stage for continued growth across our franchises in 2022. Now, let me turn the call over to Emily for a financial update. Emily

Identification in preparation of additional centers globally are on track and could you see effort to accelerate patient screening and identification activities in enriched high risk populations continues to progress well.

In conclusion the.

The commercial team is off to a strong start and has set the stage for continued growth across our franchises in 2022.

Now, let me turn the call over to Emily for a financial update.

Emily.

Emily Hill: Thanks, Eric. I'm proud to report that PTC has once again delivered excellent results with COVID-19. With strong commercial performance and a number of potential near-term value drivers expected in 2022, we are looking forward to an exciting year. Our strong global commercial infrastructure continues to support year-over-year revenues, and we are well positioned for continued geographic expansion.

Thanks Jack.

You can see has once again delivered excellent results okay.

Strong commercial performance in a number of potential near term value drivers expected in 2022.

The next meeting.

Our strong global commercial infrastructure.

Year over year revenue.

We are well positioned for continued geographic expansion.

Emily Hill: Our growing sales revenue base combined with revenue to cover expected milestones and policies allows us to continue to invest in innovation. I will now turn to the financial results for the first quarter of 2020. Please refer to the press release issued today for additional details. Beginning with our top five results, total revenues were $129 million, compared to $118 million in the first quarter of 2021. Of this, the DMV franchise produced $128 million in revenue, compared to $9 billion in the first quarter of 2021, which includes some final revenues of $79 million in the first quarter of this year.

Our growing revenue base from behind Us.

I think milestones and will allow us.

To invest in innovation.

I will now turn to the financial results from the first quarter.

Please refer to the company issued two bonds for additional detail.

Beginning with our top line was off in the first quarter.

Total revenues 449 months.

102 million for the first quarter.

Hi.

Our DMD franchise begin to 128 million women.

Compared to <unk> 91.

Got it.

This includes 10 final revenue from 79 million in the first quarter.

That's compared to $47 million in the first quarter of last year.

Emily Hill: I've compared 47 million in the first quarter of August, and while revenue was $49 million in the first quarter of this year, I'll compare it to $44 million in the first quarter of 2021. Total revenue for the first quarter of 2022 also included 19,000 in cooperation and royalties. The total sales of our services are approximately $226 million.

Plasma revenue for 49 lung the first quarter of this year.

44 million in the first quarter comes from.

Total revenue for the first quarter of 2020 also included.

Winnie collaboration on layoffs.

Cancel difference this quarter than the clock Tonight.

Okay.

Emily Hill: In the first quarter of 2021, we recorded $7 million in royalty revenue, in addition to a $20 million milestone payment that was recorded as collaboration revenue. And Ruby Hardy revenue is off the chair, and it's expected to continue growing revenue and reimbursements from online throughout Europe and outer markets in the future! As a reminder, PTC is eligible to receive a $50,000,000 sales-based MAPM payment from Moush, and annual sales have ever since reached $750,000. Non-GAAP R&D expenses were $127 million for the first quarter of 2022, excluding $13 million in non-cash stock-based competition expenses.

In the first quarter of 2021.

My arms with Albemarle in addition to $20 million Boston Portland.

Great.

People ask me revenue is that Karen this focus.

Pricing and reimbursement.

Another.

Another market that's quite a few.

As a reminder, PTC is eligible to receive a $50 million milestone payment from Roche in Europe .

2018 reached 759.

non-GAAP R&D expenses 127 million for the first quarter from 2000 <unk>.

Excluding 13 million of noncash stock based compensation expense.

Emily Hill: Compared to $121 million for the first quarter of 2021, excluding $14 million in non-cash basis compensation. Non-GAAP FPMA expense was $60 million for the first quarter of 2022, excluding $14 million in non-cash copies of competition expenses, compared to $49 million in the first quarter of 2021. Unknown Applicant, Costs, cash equivalents, and marketable securities total $588 million as of March 31, 2020, compared to $717 million on December 31st, 2021. I now hand the call over to the author to restart our session in one minute.

Compared to $121 million for the first quarter 2021.

14 months.

Okay.

non-GAAP.

<unk> 69 for the first quarter, excluding $14 million.

Sure.

Compared to $49 million from first quarter 2021, excluding 12 nine months.

Compensation expense.

Cash cash equivalence and marketable securities totaled 598 now.

As of March 31st 2020.

Compared to 770 <unk>.

Sandy.

Good morning.

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

Question one.

Okay.

Emily Hill: Ladies and gentlemen, if you have a question or a comment at this time, please press the star 1 key on your touchtone telephone. If you have a question, an answer, or if you wish to remove yourself from the queue, please press the pound. Our first question comes from Eric Joseph of JBC. David, good evening. Thanks for taking the question. Thank you guys for coming to the quarter.

Ladies and gentlemen, if you have a question for Kevin.

Press Star one key on your Touchtone telephone if youre a question and answer or do you wish to move yourself from the queue. Please press the balance sheet. Our first question comes from Eric Joseph with JP Morgan.

Yes.

Hi, Good evening good evening guys. Thanks for taking my question and congrats on the quarter I guess, just one on Translarna on a couple of in the pipeline.

Operator: I guess I just want to translate what I read in a couple of pipelines. First, just a quick... The performance of this quarter is not talking about any sort of headwinds related to sales in Russia at all.

First just.

I guess with.

The performance this quarter is talking about any sort of headwinds related to sales.

Russia at all.

Eric Joseph: And are you guiding at this point in terms of how the cadence of revenue might perform in, might proceed in the second quarter with the reiteration of sort of the top lines in the DMZ franchise? And then secondly, as it relates to study 041, I'm just wondering if you could kind of compare or contrast the primary endpoint being used in this study here compared to ACT-E and D. You're looking at a 12-mode change in fixed-minute walk distance compared to just a change in fixed-minute walk.

Are you guiding at this point.

In terms of how the cadence of revenue might perform in my preceding the second quarter with the reiteration of.

Top line from the DMD franchise.

And then secondly, as it relates to study or <unk> 41.

Just wondering if you could kind of compare.

The contrast in the <unk>.

Primary end point being used in this study compared to act DMD.

Youre looking at global change in six minute walk distance compared to just change in six minute walk is it correct to assume that you are.

Eric Joseph: Is it correct to assume that you're assessing, you're taking multiple intervals in between baselines every two weeks, and in that case, how provably are you assessing system block business? Yeah, thanks everyone for the questions. Before I turn it off, Yeah, so I, you know, obviously.

You are assessing.

You are taking.

Multiple intervals between baseline in two weeks.

In that case tougher, but when youre assessing system blockbusters. Thanks Pat.

Yes, thanks for.

For the question.

Trends.

Yes.

Obviously.

Unknown Executive: In Russia, it's a volatile situation, and we're obviously closely watching as it unfolds. And, you know, we plan, you know, obviously we plan accordingly on how best, if necessary, to adjust the date we. We've been able to ensure continuity of treatment for all the patients, and we've been focusing on that. The other good point, I think, is that we've also been able to collect receivables. And currently, as a consequence of this, in terms of revenues, it's been business as usual. Unknown Speaker So our exposure and our, you know, with our total revenue guidance, it was a really effective ride. Unknown Speaker.

In Russia, it's a volatile situation and we're obviously closely watching.

As it unfolds.

We plan obviously to.

We plan accordingly.

If necessary to adjust.

The business, but what are kind of but probably as you know the sanctions do exclude exclude medicines and we've been really focusing on the.

The continuity of treatment.

The boys and young men, who have not.

Sure.

In the REIT.

<unk>.

I think the good news.

As to date.

We've been able to ensure continuity of treatment for all their patients.

And we've been focusing on that the other good points I think is that.

We've also been able to be collecting the receivables currently.

As a consequence.

In terms of revenue with student.

Business.

Business as usual.

So our exposure in our.

With our total revenue guidance isn't really affected right now.

Unknown Executive: So it's hard to, you know, we haven't seen any issues with that. Matt, do you want to talk about it at DMT? Eric, thanks for the question. To answer your question regarding the use of the model for Study 041, it's exactly the same as you mentioned. It obviously not only includes the baseline and final six-minute walk distance, but it also includes information collected at all the other time points, which makes it a much more robust approach to data analysis.

So that's so it's hard to we haven't seen.

Any issues with that.

Good.

Well, Matt I wanted to talk about the TMT.

Yes sure Eric Thanks for the question.

Your question regarding the use of the model for study one for one it's exactly to do as you mentioned, obviously not only into the baseline.

Our final walk.

Instead it also infer.

Information collected all of the other side, which makes it a much more robust approach to data analysis. That's typically why one would use our model of that towards the other thing. It does given that I think you asked about having this study visit time points.

Unknown Executive: That's typically why one would use a model of that sort. The other thing it does, given that I think you asked about having the study visit time points, being that we had previously discussed that, as a result of COVID, some of the visits occur outside the window. By using a model, you can also not only include the specific observation but also the time at which an observation is made. The benefit of the model is that you not only have information on the walk distance but also the time at which that distance was collected.

We had previously discussed.

Some of the visit right outside the window.

By using our models also.

Observation, but also.

<unk> made and some of the benefit of our model is that you've got all the.

Unknown Executive: Again, just giving you a lot more information in the overall analysis. That's very helpful news. Maybe just one follow-up on page 41. As well, in terms of patient demographics by ambulation at baseline, I know you're stratifying for different ranges of 6-minute walk distance at baseline, 300 to 350, 350 to 400, and so on.

Information on long distance, but also.

With that distance was collected so again, just giving you a lot more information and your overall analysis.

That's very helpful. Maybe just.

Maybe just one follow up on <unk> 41.

As well in terms of.

Patient demographics by ambulation at baseline I know youre satisfied or different.

Ranges in six minute walk distance that baseline 300 to 350 to 400.

Unknown Executive: Are there any quotas associated with those? I'm so excited for today.

Are there any quarters.

Associated with those.

Ranges like are you choosing to accrue a certain proportion of patients that baseline average age three to 53.

250 or.

Other other interest thanks.

Yes.

Or are you can you say at this point.

<unk>.

The average baseline.

Unknown Executive: Walk-distance that you would expect for a patient that would be evaluated to modify the pediatric group. Thanks. Yes, sure. So the overall study population, as we've talked about, is about 360 boys, and then there is that modified population you mentioned that has the specific block distance, and that would be 185 boys.

Walk distance that you would expect for patients that would be evaluated the modified intent to treat group. Thanks.

Sure.

Yes.

Matt.

Yeah sure. So the overall study population as we've talked about 306 boys and then there is that you mentioned that.

Hi.

Terrific walk distance that would be $185.

Unknown Executive: We're not telling you exactly what the mean baseline values were, but those are the three populations, the 360 and the 185. Okay, great. Well, thank you guys for the great questions. And the other question that Eric had is just in terms of how we're thinking about... Revenue Growth for Tenderloin Over 2022, we think. So what we think is it's going to be, you know, last year was obviously driven by geographic expansion, new patients, stars, high patients, compliance, and the expanded age that we got on the label, Brazil. We also anticipate strong revenue growth for TransLino franchising in 2022.

Not commenting as probably as I think about the mean baseline value is work with those targets.

The 2016 and 185.

Okay, great well, thanks again for taking my questions.

The other question.

Just in terms of how we're thinking about.

Revenue growth for.

Trendline over 22020 through what we see.

So we think it's going to be.

Last year, obviously, it was driven by geographic expansion, new patient start high patient compliance and expanded we expanded Asia, if we got a typo in Brazil.

We also anticipate strong revenue growth for transplant of franchises.

'twenty, two that's going to be driven by the acceleration of the foot.

Turning to new markets.

Optimizing our presence.

The current market and then driving access for all eligible patients in the new markets and the ongoing expense and the current market. So that's our focus so we plan, we think that's going to be another strong year for the brand.

Unknown Executive: That's going to be driven by the acceleration of the footprint and new market, optimizing our presence in the current market, and then driving access for all LGO patients in the new markets and ongoing access in the current markets. That's our focus. So we plan, and we think that's going to be another strong year for the franchise. Your next question comes from Kristen Kluska with Caterpillar. Hi. Hi everyone. This is Rick on for Kristen.

Thank you. Our next question comes from Christian Costco with materials.

Kristen Kluska: Thank you for taking our questions. We've just got two for you here. In the MITEI trial, can you talk a little bit about the seizure run-in measurement? Given that there are multiple types of seizures the patients can have, some of which are more observable than others, how are you measuring seizure activity? We'd be interested to know how this approach sharing a lead-in is tailored to the types of seizures that these patients are typically experiencing. Oh, man.

Hi, Hi, everyone. This is Brad on for Christian. Thank you for taking our questions. So I just got two for you here in the <unk> trial could you talk a little bit about the seizure run in measurement given that there are multiple types of seizures patients can have some of which are more observable than others. How are you measuring seizure activity we'd be interested in know how does.

Approach during the lead in is tailored to the types of seizures that these patients are typically experiencing.

Okay.

Matthew Klein: Yeah, absolutely. So, the MITEI trials we've talked about in our global study looking at the effects of titquinone on mitochondrial disease-associated seizures, which is a highly morbid and common symptom of mitochondrial disease, and about 30 to 50% of all patients with mitochondrial disease have seizures, and these are typically refractory antipyelagic medications that are commonly given for the simple reason that common antipyelagics don' In fact, many of them actually heighten occupational stress, which is what's causing seizures in these children.

Yeah, absolutely so be it.

There might be trials, we've talked about is a global study looking at the effects of a ticket.

Mitochondrial disease associated seizures, which is a highly morbid in common.

Given the mitochondrial disease.

About 30% to 50% of all patients with mitochondrial disease pads seizures and these are typically refractory to anti <unk> anti epileptic vacations that economy given for the simple reason that common anti epileptics don't target the energetic pathways.

<unk> are positive.

Seizures and other kinds of these patients in fact, many of them actually heightened.

Say in distress, which is what's causing seizures. These children. So while you may have some benefit of anti epileptic.

Matthew Klein: So while you may have some benefit from the antiepileptic, it's offset by the increased occupational stress exacerbating the seizure pathology. And as you pointed out in your question, these children do have multiple seizure types. So the focus for the run-in phase into the primary endpoint is observable motor seizures, for the exact reason you highlighted, which is you want to make sure that the parents can observe and count those. And so at the base, what we do to track the seizure changes, we provide the parents with a diary.

Offset by the increased oxidative stress exacerbating the seizure.

Okay and as you pointed out your question. These children do have.

Multiple seizure types, but the focus for the run in phase as the primary endpoint is the observable motor seizures to be exact reason, you're highlighting which is you want to make sure that the parents can observe and content and so the base what we do track the seizure changes let me provide patients.

Matthew Klein: They undergo extensive training with the seizure diary, including a vocabulary list in which we capture the different types of seizures they observed in their children. And we highlight that we are counting the observable motor ones, the ones they see that involve motor activity. And so these are calculated during the run-in phase.

Aaron's with a diary they undergo extensive training with the seizure diary, including a vocabulary list, which we capture that tissue types of seizures. They observed in their children and we highlight that we are accounting the observable odor.

<unk> seen that evolve motor activity.

And so the fees are calculated during the front end phase, we're requiring minimal fixed observable motor seizures that will then serve as the baseline comparison following the six months of either.

Matthew Klein: We're requiring a minimum of six observable motor seizures. That will then serve as a baseline comparison following the six months of either, I'm sorry, 24 weeks of either methiconin or placebo therapy. Then we'll change; we'll compare the monthly rate of solidly placebo or methiconin with that baseline frequency. But again, the primary endpoint will be observable motor seizures, and the secondary measures will capture other aspects of post-seizure. understood.

24 weeks of either <unk> or placebo therapy in men will change will compare the monthly rate of.

Following placebo or particularly on with that baseline frequency, but again the primary endpoint will be observed for motor seizures.

And the secondary endpoints will capture other aspects of <unk> biology.

Matthew Klein: Thank you. Thank you for that. And maybe just one more.

Understood. Thank you. Thank you for that and maybe just one more.

After recently initiating the phase III pivotal HD trial is there anything you can say about ongoing enrollment pace or performance of clinical sites versus expectations would really like we'd really be interested in getting an idea of how the early stage of trial enrollment has gone. Thank you.

Matthew Klein: After recently initiating the Phase II PIVOT-HD trial, is there anything you can say about ongoing enrollment pace or performance of clinical sites versus expectations? We'd really be interested in getting an idea of how the early stage of trial enrollment has gone. Thank you.

Yeah. Thanks, Steve So we recently.

Matthew Klein: So we, you know, we recently initiated this. Obviously, you know, what our plans are is it's a year-long trial that's broken up into a 12-week part and then going on for the rest of the year. And what we said is that our anticipation is that we'll have the results from the 12-week portion by the end of the year. So, that's going to be looking at, you know, the treated versus placebo, looking at, you know, the level of, you know, obviously, safety, and then looking at the levels of HPT, RNA, and protein in the blood, in the cell blood, you know, to get that information, and then looking Thank you. The next question comes from Harold with RBC Capital. Hey guys, good afternoon. Thanks for taking my questions. My first one is on GTAA-DC.

Initiated.

This trial so.

Obviously, you know what.

Our plans are.

Three year long trial.

Broken up into a 12 week part and then going on for the rest of the year.

And what are.

What we said is our anticipation is that we'll have the results from the 12 reports.

By the end of the year that kind of be looking at.

Looking at page.

The treated versus placebo looking there.

The the level, obviously safety and then looking at the levels of HP.

T RNA and protein in the.

Well I can smell blood, we're able to get.

That information and then looking at also.

Biomarkers such as <unk>.

Okay.

He is well known.

MFS.

And in June .

In the CSF.

Thank you.

Our next question comes from perhaps with RBC capital markets.

Yes.

Hey, guys. Good afternoon, thanks for taking my questions.

My first one is on.

GTA ADC.

Harold: It sounds like you've had some productive discussions with CHMP. I was wondering if you could maybe elaborate a little bit more about the meetings, your confidence in a positive recommendation there, and then, I guess, as we think about the launch preparation that you discussed a bit, can you elaborate a little bit more on maybe just the numbers of centers, of these neurological centers that you expect to launch with and the degree to which they've already identified patients, or will the kind of additional launch engagement kick off the screening process? And then I have a follow-up on that. Thanks.

It sounds like you've had some productive discussions with <unk> I was wondering if you could maybe elaborate a little bit more.

About.

The meetings you're confidence in a positive recommendation there and then I guess as we think about the launch preparation that.

First a bit can you elaborate a little bit more on maybe just the numbers of centers of the neurological centers that you expect to launch with <unk>.

The degree to which they've already identified patients or will be kind of initial launch engagement kickoff. The screening process and then I had a follow up on <unk>. Thanks.

Thanks.

Unknown Executive: Sure. Yeah, thanks for that question. So, obviously, we talked about, and we told you that we will be having our CHNP opinion in May. And just to remind everybody, you know, AADC is obviously an ultra-orphan, highly morbid, and fatal TV actor disorder where you see patients, you know, patients that lack dopamine, and as a consequence, their growth is arrested where you can see in the severe form of patients, they're unable to hold their heads up, sit, roll, roll over, stand.

Sure.

Yes, thanks for that question so.

Yeah, we talked about.

We will be happy now.

We will have to see.

Key opinion and Matt.

And just to remind everybody.

ABC is obviously, an ultra orphan highly morbid.

Television actor, So order, where you see fit.

Sure.

Patient.

So for me and as a consequence, the growth arrested where you can see in the severe form of patients.

Unable to hold their head up.

Fifth row rollovers Stan.

Unknown Executive: It's, you know, much like you've seen in the severe type of patient, quite similar to that. And as we said in our recent disclosure, we announced that we had completed, and we've been working with the CAT, which is the Committee for Advanced Therapy, and that's the committee that's part of the CHNP that looks at, you know, gene therapy. So we recently said that we had both a scientific advisory group meeting, as well as an oral explanation, and that we successfully completed those, of those, and that, as a consequence of that, we anticipate that they'll be sending their final opinion in May, so we felt good about it. Maybe Matt, do you want to, Matt was there leading the charge, do you want to talk a little more, Matt?

Much like you've seen in the severe severe types if I may.

Quite similar to that.

As we said in our recent disclosure.

Now that we've completed.

We've been working with the cap if the committee for advanced therapies when Thats The committee.

C H M C.

That looks at.

Looking at the fair.

So we so.

We said that we had.

Both the scientific Advisory group.

Meeting as well as oral explanation in that we successfully completed those.

And that is.

The consequence of that we anticipate that there will be.

Extending their final opinion.

In may so we felt good about it maybe Matt do you want to.

Matt was there.

Leading the charge that you want to talk a little more Matt.

Matthew Klein: Thanks for asking the question. So, you know, obviously, we're optimistic about the positive opinion today, and a lot of that's based on the content of the meetings. I think a lot of the meetings focused on details around the label, which obviously, you know, this is probably not going to be the end of the process in heading towards a positive opinion. And obviously, we look forward to just being able to bring this therapy to patients.

Yeah sure Thanks, Brian for the question.

Obviously, we're optimistic.

About a positive opinion in a lot of that is based on the content of the meetings I think a lot of a lot of the meeting discussion focused on details around the label, which obviously gives us a sign that we're near the end of the process and heading towards a positive opinion.

Matthew Klein: The data collected to date is very compelling, and the ability to show that we've been able to provide treatment to kids who have no motor activity, provide the gene, and now they are, in many cases, able to sit and walk and perform as healthy children at that age. I think the other important part of the data is the durability, which is a really important part of the package.

And obviously, we look forward to it.

Being able to bring this therapy to patients the data collected data.

Okay.

<unk> showed it.

I will provide you indicated you have no motor activity provides athene and now they're in many cases stable two chips and guac.

Requirement as healthy southern light.

The other important part of data availability.

It's just really important part of the fact that we have follow up.

Hey, guys.

10 years selling.

Our ability.

And are there other benefits of the drug.

Matthew Klein: So we have follow-up data from 6, 7, 8, 9, even up to 10 years showing durability of the motor benefit and other benefits of the drug. I think we're also really excited that this would, as you said, be the first ever diagnostic gene therapy for the brain. I think that's really an important advancement in the entire field of gene therapy, and we cannot think about marrying a common pediatric and adult neurosurgical procedure, instead of a tactical guided surgery, with the delivery of gene therapy to the brain where it's needed most.

So really excited that fiscal seems that'd be the first ever directly models in each of the brain I think thats really an important advance for the entire sale of the gene therapy that we can now think about marrying a common.

Pediatric and adult neurosurgical procedure set in the tackle private surgery with the delivery of therapy to the backlog.

Okay Brian .

Matthew Klein: I'll leave that there for the time we need for our preparation for launch and the surgical and neurologic centers there. Yeah, so maybe, you know, as Matt just alluded to, we were excited about completing these and have been working hard to get ready for launch preparation. And so, I think there's been, we've been doing this for quite some time, both getting the neurosurgical centers ready, as well as for patient identification, and really doing a lot. As everyone knows, this is a relatively new disease, so you have to identify the patients. And we've been looking now and finding patients, and that's been accelerating as well. We've done over 100 screening programs in 20 different countries, and we're finding them in all countries.

Most.

Is that that's a segue to our preparations for launch in the.

Surgical.

Centers of excellence.

Yes, so maybe.

Matt just alluded to.

So we were excited about.

<unk> been working hard to get ready for a launch preparation.

And so I think there has been we've been doing this for quite some time, both getting the neuro surgical centers ready as well as for patient identification and really doing a lot of screening.

One note this is a relatively new.

New disease, So you have to.

Densify the patients and we've been looking now and finding patients and thats been accelerating as well we've done over $100 screening programs in 20 different countries have been finding member countries. So we're really excited about so Eric do you want to talk a little bit about all of them.

Stuart Pauwels: So we're really excited about this. Eric, do you want to talk a little bit about all the efforts that have been going on? Yes, certainly, Stu. I mean, the launch preparations themselves are progressing extremely well.

Going on.

Yes, Sir certainly assume I mean, the launch preparation themselves are progressing really well, we've been focusing on accelerating disease agitation patient identification and that's been going on already for a number of years.

Eric Pauwels: I mean, we've been focusing on accelerating disease education and patient identification, and that's been going on already for a number of years, but to your point, Brian, preparation of surgical treatment centers has been really an important part of our most recent efforts, and in particular, we've been working with many of the top key opinion leaders, both neuropediatric neurologists as well as neurosurgeons in preparation for that. So to answer your question really simply, we are looking to ensure that there are multiple centers in each of the main countries that will be ready, that are ready now, and will continue to be ready, and we're going to continue to expand in each one of these major markets to ensure that we have as many centers over time.

But to your point, Brian preparation of surgical treatment centers have been really an important part of our most recent efforts and in particular.

Been working with many of the top.

Opinion leaders, both the pediatric <unk>.

And the neurologists as well.

As neurosurgeons in preparation for that so to answer your question really simply we are looking to ensure that there are multiple centers.

And each of the main countries that will be ready that are right now and we will continue to be ready and we're going to continue to expand in each one of these major markets to ensure that we have as many centers.

Over time, one of the things that we do know is that as we find patients and as we treat them.

Eric Pauwels: One of the things that we do know is that as we find patients and as we treat them, and the more we provide disease awareness and education when a treatment is available, and the families and the patients see this, we certainly will have more and more demand, and we'll continue to expand, if you will, the number of centers that we have, not only in Germany, in France, in Italy, of course, the UK, Northern Europe, and many of the other So we certainly are going to do as many centers as possible. We'll have multiple centers in each of the main countries, if possible. That's super helpful; thanks.

And the more we provide.

<unk> disease awareness and education when treatment is available and the families and the patients.

We certainly will have more and more demand and we.

We'll continue to expand if you will.

And there are a lot centers that we have.

Not only in Germany and France.

In Italy.

UK, Northern Europe , and many of the other markets that will have early access programs. So.

We certainly are going to do as many centers as possible, but we will have multiple centers in each of the main countries on the block.

That's super helpful. Thanks, and then maybe just a quick one on $5 eight.

Unknown Executive: And then maybe just a quick one on 518. The phase two study was posted on ClinTrials this morning. And I guess we're curious what the SMV is gonna be looking for to make the recommendation to escalate to the 20 milligram dose for part B. That's just safety, we'll be looking at knockdown, and is there a goal there?

The.

Phase II study was posted the Quin trials. This morning, and I guess I'm curious what the SMB is going to be looking for to make the recommendation to escalate to the 20 milligram dose for part D is that just safety will be.

Yes.

Down and is there a goal there and I know also you guys have talked about volumetric MRI. That's one point that could be used for accelerated approval. We didn't see that listed in the posting wasn't sure. If that was just because that's the thing that will be in part b or if theres been any change too.

Unknown Executive: And I know you guys have talked about volumetric MRI, that's one point that can be used for accelerated approval. We didn't see that listed in the posting, and I wasn't sure if that was just because that'll be in part B or if there's been any change to the endpoints you view as being key there for accelerated approval. Thanks. Thanks for the question. I think from the first part of the question, we're really looking for a reduction, and obviously, besides safety and efficacy, we're also looking at the biomarkers, the reduction in terms of the levels of HTT, of RNA, of protein in the blood, and what happens in the CSS, so that in terms of PK levels as well, so we will define what those levels are, right?

The endpoints you view as being key to air for accelerated approval. Thanks.

Sure. Thanks, Chris.

I think from the first part.

I assume it's really we're looking for a reduction in.

Obviously besides safety.

Thank you. We're also looking at the Biomarkers the reduction in terms of the level of.

Okay.

Our <unk> protein in the blood as to what happens in the CSF.

In terms of PK levels as well so that we will define what those levels are.

Unknown Executive: We saw a two-and-a-half to three-fold increase in the CSF levels of the blood in the Phase I studies. Is that the same that we see in terms of what we did? Well, based on those numbers, what we're looking for, how we titrate, whether we need to or not, and what levels we should use to titrate the compound.

We saw two and a half three fold increase in the CSF follows the blood in the phase one studies.

Same.

Okay.

In terms of what we do.

Two it will based on those numbers, but we're looking for.

<unk>.

Great.

Whether we need to or not.

What level could reduce the tax rate.

Uh huh.

Unknown Executive: In terms of the MRI, Matt, you want to talk a little bit about that? Yeah, sorry, so Schwartz, you can just follow up on the students' point of reference. It will be a combination of the safety evaluations for the VSMBA and what we're seeing in terms of the levels of reduction, hunting to mRNA and protein, as we said, are long-targeting at 30 to 50 percent reduction range. So, how close are we with the first two doses, and then do we need to titrate the molecule and go to an additional dose, and then, of course, marry that with the safety evaluation from the VSMB?

In terms of.

The MRI, Matt you want to talk about that.

Yes, sorry.

Sure and just to follow up on Steve's point, Brian said, it will be a combination of the safety evaluation for the S&P, what we're seeing in terms of the level of production in Huntington mrna and protein as we've said all along targeting 30% to 50% reduction range.

How close are we with the first few doses and then.

Do we do we need to.

I traded below the molecule and go to additional dose and then of course Mary that safety evaluation from the SMB in terms of clinical trials Dot Gov, Youre correct, but listen there is for that first 12 week portion of focusing on the pharmacology.

Matthew Klein: In terms of clinicaltrials.gov, you're correct. What's listed there is that first 12-week portion focusing on the pharmacology and PKTD relationship, and volumetric MRI will be tracked, and that's going to really be an end point in the second part, right, the nine-month continued remote-controlled focus on biomarkers. Really helpful. Thanks again.

It can be.

Relationship.

And volumetric MRI will be tracking that but thats going to really be an endpoint in the second part.

Nine months continued controlled focus on Biomarkers.

Really helpful. Thanks again.

Unknown Executive: Our next question comes from Joseph Tomey with Cowen. Good afternoon, and thank you for taking the questions. Maybe one on AADC in the U.S., maybe what remains to be done ahead of submitting that VLA? Have you been able to meet with the FDA and have them plan off of those surgeries that have been completed?

Our next question comes from Joseph told me with Cowen and company.

Hi, there good morning, or good afternoon.

Good question.

Maybe one on an ADC.

In the U S. Maybe what remains to be done to submitting that internally.

Have you been able to meet with the FDA and the synergies.

Sure.

Joseph Tomey: Yeah, thanks for that. So, with the ADC, as we said, obviously, we're in the last stages of completing what we needed with the CAT and the CHMP. So, we felt we had that completed, and we think that's going to be quite helpful for the FDA. And so, based on that, the next steps, Matt, why don't you go through what our plans are with the VLA. Yeah, absolutely, Joe

Yes, thanks for that.

So with the ADC as we said obviously.

We're in the last throes of completely.

What we needed with the us with the cat in the sea HMT. So we felt we could.

We've got next Cleveland, we think that's going to be quite.

Quite helpful for the FDA and so based on that.

The next step Matt months through our plants.

Okay.

Matthew Klein: Thanks for the question. As you said, we... wanted to get to the finish line in Europe and obviously be able to leverage all the funds we've made in the regulatory interactions with Europe and really use those to enhance the package for the FDA. And as we said, the plan will be to meet with the agency, align on this mission package, and move forward.

Yeah, absolutely thanks for the question.

Okay.

We said.

Okay.

To get to the finish line in Europe , and obviously be able to leverage all the filings we've made and the regulatory interactions, but Europe is used.

Use.

To enhance further the package for the FDA.

Matthew Klein: We'll look forward to meeting with the agency and then moving forward with the next step. And maybe some more financial questions. I know a lot of the acquisitions that you did over the past couple of years had some pretty effective up-fronts, but they came with some milestone payments on enrollment or successful data or approval. So are some of those milestones baked in to the 2022 financial guidance? And maybe if you could just highlight the ones that we should expect, that would be very helpful.

As we said the penalty to meet with the agency align on this submission package and look forward to meeting questions submitted.

We will look forward to meeting with the agency and then moving forward with the next day.

Perfect that makes sense and maybe more a financial question.

I know a lot of the acquisitions that you did over the past couple of years had some pretty attractive upfront I think came with some milestone payments on enrollment or successful data or approvals. So.

Are some of those milestones baked into the 2020 to financial guidance, maybe if you could just highlight the ones that we should expect that very helpful. Thank you yeah, yeah sure. So yeah.

Unknown Executive: Thank you. Yeah, yeah, sure. So, yes, they are baked in. And Emily?

Yes.

And then.

Emily.

Emily Hill: Yeah, thank you. Thanks for the financial question. We do have a payment due for success in AADC, and that's $70 million expected in 2022. And then for PKU, we also expect to pay a $30 million developmental milestone for the completion of enrollment in the clinical trial in 2022. Thank you very much. Very helpful.

Thank you thanks for the financial question.

We do have a payment to <unk>.

Success in ADC.

And that $70 million expected in 2022.

Then.

PKU.

Thanks Seth.

They have $30 million developmental milestones.

<unk> of enrollment of the clinical trial and Tony.

Perfect. Thank you very much very helpful.

Unknown Executive: Yeah, on the flip side, I just want to remind you that in our revenue guidance, we have a $50 million milestone from Roche expected for a certain number of sales thresholds, and there's the potential to reach up to 100 million milestones for additional thresholds. Okay, thank you guys. Our next question comes from Gina Wang with Barclays. Thank you for taking my questions. I have three questions.

On the flipside I, just remind you that.

Revenue guidance, we have a $15 million milestone from Roche.

Certain of risky sales.

There are some potential.

$100 million milestone for additional questions.

Okay.

Hey, guys.

Our next question.

Our next question comes from Gena Wang with Barclays.

Gina Wang: The first one is regarding Inflaza. I just want to clarify that seven-year orphan drug exclusivity should expire in 2024, and also assume an additional six-month extension based on the label expansion to younger patients, and also no more protection after 2024. So that's the first question. The second question is regarding Transplanta. What kind of data do you need to submit every year to receive a renewaler in Europe?

Thank you for taking my questions I have three questions. The first one is regarding in Florida.

Gina Wang: And my third question is regarding the PIVOT HD trial. Since you will collect data, Huntington protein data, both in the blood and the CSS, and based on what you've learned so far, do you expect a similar percentage reduction in Huntington protein in the CSS versus blood? Great, so... Um, so I'll take the first one in terms of loss of exclusivity of the plaza. That is, yes, you're correct, it

Just want to clarify that seven year orphan drug exclusivity should be expired in 2024.

And also even assuming additional six months expansion based on the label expansion to younger patients.

And also no more protection after 2024.

My first question My second question is regarding thanks Lana.

Type of data every year, you need to submit to receive needs.

When you were in Europe .

And my third question is regarding.

HD trial listings, you will collect data Huntington protein data boasting a blood and CSF and based on what you've learned so far.

That's similar.

Such a reduction in Huntington protein.

G protein.

DSS, there's just a lot.

Hey, Craig so.

Unknown Executive: Obviously, we're doing some work evaluating our options in order to do that, so that we, you know, in order to maintain that. And obviously, we have a number of programs that we're working on to retain patients, which we're, you know, obviously optimistic about because we provide patient support services around the clock to both the patient and the caregiver community. And then we got out of evaluating all options to defend the influence of brands, including leveraging patient support programs, driving the channels pulled through from the specialty pharmacy partnership, and then leveraging our key relationships with the contracts and payers.

So.

First on in terms of loss.

Liberty.

The Plaza that yes, you are correct to assume 2024, obviously, we're doing some work through evaluating.

Sure.

In order to do that.

Oh.

So that in order to maintain that and obviously, we have a number of programs that we're working on to retain patients.

Patients were.

Obviously optimistic about a lot because we can provide patient support services around plaza.

With the patient caregiver community.

We are.

Evaluating all options.

Being plaza brands brands, including <unk>.

Leveraging the patient support programs.

Driving the panels from the specialty pharmacy.

Partnerships leveraging.

Key relationships with.

The contract tenure.

Unknown Executive: So, you know, you might probably be aware of this in the rare disease market, patients are actually relatively loyal, loyal in that their pricing discounts are often offset by patient support programs. In terms of... TransLARN and what we put in, Matt, why don't you go through that a bit.

So you might probably be aware of this.

These market patient starts are actually relatively long.

Loyal and less generic pricing discounts are often offset by patient support program.

In terms of.

Learn and what we put is Matt wants to go through that.

Matthew Klein: Yes, certainly. Thank you for the question, Gina. So, for the annual renewal, it includes safety data that's collected from our post-marketing safety registry as well. And we include data from the STRIDE registry to provide evidence of clinical benefit.

Certainly thanks for the questions Gena for the annual renewal is basin.

As safety data collected from our post marketing safety registry as well include data from the stride registry to provide evidence of clinical benefit.

Matthew Klein: So, it's basically information that continues to support a favorable benefit-risk balance, which is obviously the key of what the European authorities are looking for to continue the renewal. And then your third question was HC blood and CSF, right? So I think it's an interesting question from the point of view of when you think about, Um, you know, what's occurring within the cell, that, you know, you know, obviously, right, where we're, you know, altering splicing, we look at the reduction of the both RNA and then the reflexive of what's going on in the protein, you think you have a good sort of juxtaposition of seeing how much, what's the exposure and what's the reduction, right?

Basically inflation continues to support a favorable benefit risk.

Obviously the key.

The European authorities and looking forward to continue the renewal.

And then your third question was.

HD blood and CSF right.

So I think it is.

Interesting question from the point of view.

When you think about.

No.

Whats occurring within the.

The cell.

Obviously, we're you're altering spicing, if we look at the reduction.

And then the reflect reflective of what's going on in the protein. You said you have a good sort of justification of seeing how much what's the exposure on whats the reduction right.

Thats quite nicely.

Unknown Executive: So you see, that's quite nice. However, when you think about what's going on in the CSF and the biomarkers, I think it's almost a different measure because you're not measuring what's within a cell, right? You're measuring what's outside the cell.

However, when you think about what's going on.

Yes.

And the biomarker.

It's almost a different measure because youre not managed three.

Within the south.

If you're measuring what's outside.

Unknown Executive: And so we know there's probably a small amount and that the rest of it is probably a consequence of broken cells that lead to the amount of HTT within the CSS. So the interesting question becomes what are the changes that would occur, and so we'll monitor that. I think this will be, you know, because PTC, you know, 518 is able to go completely through, you know, to every part of the brain, this is gonna be probably the best estimate anyone's ever done in terms of saying what the effect is and what CHTT reduction in the CFF means and how fast it goes down.

We know, there's probably a small amount okay.

Okay.

Okay.

And then the rest of it is probably a.

Broken out.

Right.

The amount of HPT within the CSS.

So the interesting question becomes.

What are the changes.

That would occur and so we'll monitor that and I think this will be because of PTC.

Five eight people to go completely.

Every partner right.

<unk> is going to be probably the best estimate everyone. What's.

Whats the effect of weather.

Yeah.

Yes.

I mean, and how fast does it go down.

Unknown Executive: What we're gonna learn also from this is the exposure level of the drug within the CFF and see if it maintains the same as what we saw in healthy volunteers and subjects, or is it different than what we see versus HTT patients? So we're gonna learn a lot there in terms of, really, in a very, you know, careful way where you can actually know the level of exposure and know that within the CFF, what's the consequence of altering the levels of things like HTT, you know, the secreted or due to broken cells? Because if you think about it, the reduction could be a consequence of not breaking.

What we're going to learn also from this.

Exposure level of the drug.

Within that.

I think the thing about what we saw in healthy volunteer subject or is it different than what we see.

Versus.

So we're going to learn a lot in terms of.

Oh really.

Gary.

Careful way, we disconnect Chile, no the level of exposure.

No within.

CSF with the consequence of all three.

Level.

Things like <unk>.

It'll be accretive or do the brokerage so because if you think about it with you.

The reduction to your comps.

Great.

Not breakeven.

Unknown Executive: So, you know, how you measure it and how fast it goes away might be quite interesting. Does that help you? Yes, yes, that's helpful. I'm just wondering, like, you know, does that mean we actually keep the lower baseline in the CSF? Should we actually see more sensitive change in a CSF versus blood? What do you mean by lower? We don't have any. Because in a CSF, you only have broken proteins released from the cell versus in the blood, you collect all the protein inside the cells, so then the baseline level of protein will be much higher in the blood versus in a CSF.

So what how you're measuring and how fast it goes away it might be quite good.

Does that help you.

Yes, yes, that's helpful.

Just wondering like does that mean, we actually giving the lower baseline in the <unk>.

Should we actually see more sensitive change in the CSF versus a lot.

What do you mean, lower we don't have any.

Like why.

Because in the CSF to only have a broken coast relief from itself versus in the blood you collect all the protein side itself. So then the protein baseline level would be much higher.

Blood versus in Spss.

Unknown Executive: That's right. That's right. So what we're looking for is the percentage, the percentage change that occurred as a consequence of that. So you, you normalize. Thank you.

That's correct that's right so what we're looking for.

<unk>.

Percentage change that occurred as a consequence of that right. So you normalize.

The change of that Youll see and HTC and you'll normalize.

But when you normalize that to what you see in the CSF.

Yes.

Thank you.

Sure.

Robin Karnak: Our next question comes from Robin Karnak. Great, thank you for taking my question. All right, okay, a couple.

Our next question comes from Robyn Carnac, because with the truest.

Great. Thanks for taking my question Alright, Okay couple.

Unknown Executive: For 8-HGC, can you just first talk a little bit about the patients you've identified, where they are, and there are questions around the launch trajectory and how quick it can be. So giving that platform would be great.

ATC can you first talk a little bit about the patients you identified where are they at in your question is around the launch.

Does that vary and how it can be so giving that platform would be great.

Unknown Executive: And given so many patients in Asia, maybe give them an update and then have a follow-up. Right? Well, I'll ask Eric to comment, Eric, and copy this. But obviously, we found patients in every country that we looked at around the globe, so there is the notion, I think people, there's a misinterpretation sometimes. I'm thinking of this is the higher nature, which I mean, there could be founders of that, but it's clearly found everywhere. Um, it's clearly found everywhere within the world.

And given so many patients in Asia, maybe give an update and then I have a follow up.

Correct.

So.

Eric.

Comment on Ericsson.

But obviously, we found patients in every country that we looked at around 12, so that there is.

So I think people, there's a misinterpretation sometime.

I'm thinking of is higher in Asia, I mean, there could be founder's effect.

Clearly found everywhere.

It's clearly found everywhere within the World Theres no countries that we haven't found it.

Unknown Executive: There's no country that we haven't found them in. And patient identification has been ramping up. You know, as we said, we've done over 100 programs, and we've begun learning how to find them. So we're accelerating in finding them as well.

And we've been in the patient identification has been ramping up.

And obviously as we said we've done over 100 programs.

And learning how to find them, so we're accelerating as well.

Eric Pauwels: Eric, you wanted to talk a little bit more about patient identification, if I may. Yeah, sure. Thanks for the question, Robin. You know, patient finding has been something that we've been really good at, and we've been seeing good progress every quarter as we've been focusing now across multiple geographies. And over the past couple of years, as Stu mentioned earlier, we've had hundreds of screening programs now in more than 20 countries. These 20 countries right here are really the focus of ours because we know they're going to be countries that have, will have access mechanisms for reimbursement for gene therapy and also have centers of excellence that can perform the treatment. So it's incredibly important that we focus our screening there.

Eric do you want to talk a little bit more about Tonight.

Yes sure. Thanks for the question Robyn patient finding something that really stood out.

Being good progress every quarter.

We've been focusing now across multiple geographies.

Last couple of years as you mentioned earlier.

Hundreds of screening programme now in more than 20 countries.

These 20 countries right here are really the focus of ours.

We're going to be countries that will have access mechanisms.

Reimbursement.

Gene therapy.

And also have centers of excellence, which can perform the treatment.

So it's incredibly important that we focus our screening there.

Eric Pauwels: We're pleased with the type of patients that we've been screening. It's been, we've been finding patients of all ages. So in terms of just, you know, very, very early in terms of two months up to their teens.

We're pleased with the type of patients that we've been creating it.

We've been finding patients all ages.

In terms of this.

Very early in terms of a few months up to their teams. So we've seen patient identification.

Eric Pauwels: So we've seen patient identification across the board, in all patient types, as well as... We're finding these patients primarily now in these high-risk population groups, particularly in cerebral palsy and epilepsy centers, and a lot of our focus has been on the key markets as well, where we have been testing or will be doing a lot of testing in these centers and finding patients. Another thing I'd like to highlight, too, is the earlier comment about centers of expertise. These neurological centers are also playing a very important role in where we are sequencing the launch.

With location across the board.

All patient types as well as.

H and severity.

We're finding these patients primarily now in these high risk population groups, particularly incredible policy in epilepsy centers.

A lot of our focus has been on the key markets as well, where we've been testing.

They've been doing a lot of testing in.

These centers and finding patients and the other thing I'd like to highlight.

The earlier comment about centers of excellence.

These neurological centers of excellence are also playing a very important role and where we are sequencing. The launch as I mentioned in Germany, France, Southern Europe , Northern Europe , where we have early access programs in access mechanisms as soon as we are doing.

Eric Pauwels: As I mentioned, in Germany, France, Southern Europe, Northern Europe, where we have early access programs and access mechanisms, as soon as we start treating patients, there is a strong interest in screening and identifying even more. So we have very active community leaders in these countries.

Treating patients there is a strong interest.

In screening and identifying even more so we are very at union leaders in these countries. So this point earlier.

Unknown Executive: So to Steve's point earlier, there is no specific market where we found more or less patients in all the key geographies, and we're very pleased with that. Breaking it down, though, can you just help us a little bit, though, feel a little bit better about, given that you're launching slowly in different countries, like where you're finding the patients and even working so hard to find them? I think that's where people are trying to go with it, it's like, you know, how is it speeding up?

There is no specific market, where we found more or less we have been finding patients in all the key geographies and we're very pleased with that.

And I think what.

Youre breaking it down though can you just help us a little bit so a little bit better about given that you're launching slowly in different countries, where youre finding the patients.

<unk> been working so hard and I think that's where I was trying to go away like.

Is it speeding up.

Unknown Executive: So I think, I think one of the, well, one of the things you have to remember that you gotta, when, when, when you have a new disease, yeah, people just misdiagnose and need to throw them into CP clinics or refractory epilepsy clinics or other places. You sort of have to turn over, and you need to sort of figure out the right algorithm.

I think one of the.

Well one thing you have to remember that you've got a win win.

When you when you have a new.

That.

So people just diagnosing these assortment of CP clinics.

Sure.

Our refractory epilepsy.

And there are other places.

Sort of have to turnover and you need to sort of figure out right now.

Define those base right and so that's why when we say we have done over 100 different programs. Because we did we use many different countries many different things and laboratories to find what's the best way to find patients and then everybody started using the best practices over.

All of that so when we say we found patients in every country. We're talking about that was that we've been purchasing it and we found them and all of them.

Unknown Executive: So when it comes to getting ready for a launch, you know, we're getting patients ready, upon approval, to line up for the search. So that's been our follow-up. That's perfect.

When it comes to getting ready for a long.

We're getting patients revenue.

Upon approval.

Two two lineup for the surgeries so that's been our rollover.

That's perfect yes.

Unknown Executive: Yeah. I'm trying to be really mindful today. I know other people are asking questions. I'm trying to be so efficient. I guess a quick question on TKU. I mean, Byron talked about how far these TKU centers are really struggling.

I'm trying to be really mindful because I know other people are asking questions I'm trying to get like so efficient I guess.

So quick question on PKU, I mean environment talk about how far do you think your centers are really struggling there they're backed up how.

How confident are you that you actually can continue to enroll in time and like I think like.

Given that backdrop and the inability to treat patients how do you feel about that and I'll just add one other question for Emily Emily you gave a lot of color around buying trends in Latam and for sale.

Clarity around how we should model.

Can you say great job staying at but just help us model.

Quarter in second quarter, a little bit more clearly.

So maybe on the first point.

I see.

Unknown Executive: They're backed up. How confident are you that you can actually continue to, you know, enroll in time? And, like, I think, you know, given that backup and the inability to treat patients, how do you feel about that? And I'll just add one other question for Emily. Emily, you gave a lot of color around buy-ins from Lebanon and Brazil.

From our point of view I think things have been.

Unknown Executive: Can you give some clarity around how we should model this? You did a great job saying it, but help us model the first quarter and second quarter a little bit more clearly. Thank you. So maybe on the first point with PKU, I think, um... From our point of view, I think things have been... Um... Unknown Speaker Well, Matt, maybe you want to talk a little bit about the Clinical Trials at PGU in Hawaii, Bengali.

Moving well, Matt you wanted to talk a little bit of color.

The clinical trials.

Unknown Executive: Yeah, sure. So, Robin, we're not seeing what you've mentioned, and I'll say that, you know, once again, we're leveraging our global infrastructure with study sites around the world and, quite frankly, a lot of pull from investigators to participate in the trial. And so our teams have done a really good job in terms of projecting and managing enrollment flows. So we're not seeing positive access incentives as being a role that has challenges. So we haven't seen that yet.

Yeah sure. So so Robyn we're not seeing what we've mentioned.

I will say that once again, we are leveraging our global infrastructure with study sites around the world and quite frankly, a lot of that's the.

Caters to participate trial and so our teams have done a really good job in terms of <unk>.

<unk> managed.

So we're not seeing positive access to centers.

Enrollment challenge at this point.

Unknown Executive: And then your last question, Robin, was, are you sort of asking about lumpiness of residents? Yeah, we've processed orders from Brazil as well, so we just want to make sure we model it correctly, because just because of granularity and how we model, you know, these orders. Do they come in exactly in the first quarter? Do they come in the second quarter?

So we haven't seen that so and then your last robbing. Your last question was are you sort of asking about lumpiness.

Yeah, Randy talked about quarters from Brookdale as well can we just want to make sure. We model. It correctly could you just give us a lot more granularity on how do we model.

Unknown Executive: How do we think about that for a lot of things? Thank you. Page PAGE of NUMPAGES www.verbalink.com, the family you want to go through.

The quarter did the comment exactly in the first quarter the second quarter, how do we think about that for Latam.

Sure.

Yes.

And when you want to go through.

Unknown Executive: Yeah, sure. I mean, we don't give quarter by quarter guidance exactly because of that lumpiness, so it is hard to give additional color for modeling purposes.

Yeah sure I mean, we don't give quarter by quarter guidance exactly cause of that Lumpiness. So it is hard to give additional color for modeling purposes, I will say that the conference.

Unknown Executive: I will say that we contemplate that guidance, that lumpiness, when we give our annual guidance, and we remain confident in our annual guidance for both the DMV franchise and the other revenues we've included. Okay, great. Thank you guys so much. Sorry to be so quick. I want to make sure everyone has good questions.

That lumpiness, when we give our annual guidance.

We remain confident.

Okay.

Both the DMD franchise and.

The other revenues.

Okay, great. Thank you guys. So much sorry to be so quick I want to make sure I would look good question. Thanks.

Thank you.

Unknown Executive: Thanks. Thank you. Our next question comes from Danielle Rowe with Remy. Hey everyone, this is Alex on behalf of Danielle.

Our next question comes from Danielle Brill with Raymond James.

Danielle Rowe: A couple of questions from us on TransLara and Celio, for one: have the EMA, like, the regulators given any indication one way or another whether market access is contingent upon Celio hitting StatSig? And how much weight is EMA putting, you know, weight, are they putting into this drive registry? And if you could just remind us about the exact timeline of regulatory actions following top-line data readout, that'd be great. Thanks. Yeah, thanks for the question.

Hey, everyone. This is Alex on for Danielle.

Couple from us on transplant on study over one half.

And the regulators given any indication one way or another whether market access is contingent upon study over one hitting stat Sig.

And how much is EMEA, putting wages are they putting into the stride registry.

And if you can just remind us of the exact timeline of regulatory actions. Following top line data readout would be great. Thanks.

Yes.

Danielle Rowe: I think, and I think we've been saying for quite some time, that we believe that the EMA really looks at the totality of the data and includes not only the trials, in the totality of them, and the results that we have in the trial but also... Results of the registry, where we're seeing a comparison of five and a half years greater walking, five and a half years better in terms of getting off the ground, and much better pulmonary function.

Yes, thanks for the question I think.

And payments.

Quite some time.

We believe that.

Yes.

We.

Really looks at the totality of data.

Hum.

And exclude.

Not only the trial.

And the totality of the data and the results that we Havent trial.

Also.

Results of the registry, where we're seeing.

<unk> five and a half years.

Or walk the year better in terms of getting off the ground much better pulmonary function.

Danielle Rowe: So those are, you know, when you think about it, those are the long-term consequences that you hope at critical endpoints will meet. And the beauty of this, by the way, is showing us that. Unknown Speaker.

When you think about it those are the long term consequences.

So do you hope that clinical endpoint.

And the beauty of the Sky breakfast.

It's showing us that.

Unknown Executive: , is showing us that the transline is having a profound effect on these kids, looking at endpoints in terms of how patients function, feel, and survive. So I think the combination of the trial data sets that we have, as well as the SREG registry, and the totality of the data is what we think is critical. Will that help you? Yeah, I mean, just to pin you down a little bit. If you're saying that you think that you have the potential to still access the market if Study04.1 does not hit status A, is that what I'm reading? Yeah, I mean, until we, you know, turn over the cards and see the data.

It's showing us that.

The trends lineup.

Profound effects.

On the.

Looking at endpoints in terms of politics.

Constant feeling survive so.

The combination of.

Of the trial.

We have a problem right.

And the totality of potatoes.

We think is critical.

So that helps you.

Yes.

Yes, I mean, just to pin you down a little bit.

You are saying that you think that you have potential.

Still access market study over one does not yet.

Is that what I'm reading.

Yes.

Turnover.

David.

Unknown Executive: It's hard to say exactly, but we anticipate that even if it's not, if we're hoping for perfection, but if there's not, if there's imperfection, we still think that this data, or if you think about this data, when looking at the totality of the data, Study 07, Study 2041, that everything, when you look at the six-minute walk test, you look at the time function test, the NSAA, falls, all the measurements that we did, it always favored Trenzano or placebo, and then you couple that with the dry results showing real-world effect, we believe, you know, we would, we certainly anticipate that this, you know, we plan to have this, that this will remain on the market regardless. All right, great, thank you. Our next question comes from Colin Bristow. Hey, good afternoon, and congrats on all the progress. Just one on 923 and PKU.

It's hard to say factory, but we anticipate that even if it's not.

Yes.

We're hoping for perfect, but it is not perfect.

Perfect. We still think that this thing if you think about this data.

When we look in the totality of the date of February seven.

Studied 2041 that every when you look at the six minute walk test.

You look at.

The time function test the MSA.

So all of those all the measurements that we do and always.

Always favoured Trent Lott over placebo and then you couple that with the right resolve showing real world effect, we believe.

And we would it.

Certainly anticipate.

We plan to have it.

We remain on the market with regard.

Alright, great. Thank you.

Colin Bristow: So the open label extension criteria was recently updated or relaxed to allow patients with 50% or greater reductions in fee levels versus previously being greater than or equal to 30%. So I just wanted to touch base on this, and can you explain the rationale and if it's at all indicative of you seeing a lower magnitude of fee reduction than you had first expected? Thanks. Yeah. Um, Matt, you want to take it? Sure, Colin.

Our next.

Comes from Colin Bristow with you.

Hey, good afternoon, and congrats on all the progress just 193 in PKU.

The open label extension criteria.

Lee I guess updated overlap to allow patients with 50% or greater reductions in sea levels versus previously being greater than or equal to 30%.

I just wanted to touch base on this and can you explain the rationale.

And is this a tool indicative of you seeing a lower magnitude of fee reduction that you've set.

Thanks.

Yes.

Matt do you want to take that.

Matthew Klein: Yeah, the purpose of a long-term extension is really just to allow patients who are in the first part of the trial to continue, and allow us to collect long-term safety data to build up the safety dossier and also, obviously, look at the magnitude of effect. That change was administrative and has nothing to do with anything we'd be seeing in the trial because we're actually not looking at any data yet or observing anything in the trial.

Sure Colin Yes, the purpose of a long term extension is really just to allow patients in who were in the first part of the trial and that's allowing us to collect long term safety data to buildup.

Okay and also obviously look at the magnitude of effect that change was administrative has nothing to be with anything can be seen in the trial, because we're actually not looking at any data yet to observe any anything in the trial I think thats just intended to allow for as many patients as possible to enter into that follow up period.

Matthew Klein: I think it's just intended to allow for as many patients as possible to enter into that follow-up period even if they maybe didn't meet the criteria to be there. It's randomized, so we could actually put them in if we want to bolster the number of patients who are collecting long-term safety data.

They maybe didn't meet the criteria to be randomized.

Randomized that we could actually put that maintenance, we want to bolster the number of patients who are collecting long term safety data on.

Unknown Executive: Okay, great. Thank you. And I'm not asking any further questions at this time.

Okay, great. Thank you.

And I'm not showing any further questions at this time I'd like to turn the call to Stuart Peltz for any closing remarks.

Stuart Pauwels: I turn the call over to Mr. Pauwels for any closing remarks. Okay, well, thank you for joining us today. I'm proud of our strong financial performance this quarter as we continue to execute and deliver on all fronts. As we discussed today, we've already progressed a number of key milestones and will continue to do so throughout the year. We're excited about the upcoming potential CHMP opinion for AAV teaching therapy, as well as the results from a number of registration-directed trials anticipated this year.

Yes.

Stuart Pauwels: We're well-positioned to continue our mission of bringing life-changing therapies to patients, and I look forward to providing updates on all our progress as the year goes on. Thanks for tuning in. Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a break.

Okay well.

Thank you for joining us today.

Proud of our strong financial performance this quarter.

As we continue to execute and deliver on all fronts.

As we've discussed today, we've already progressed a number of <unk>.

Key milestones and we'll continue to do so throughout the year, we're excited about the upcoming until Q2.

For.

<unk> therapy as well as the results from a number of registration trials.

They did this year.

We are well positioned to continue our mission of bringing life changing therapies for patients and I look forward to provide an update on all our progress since the year goes on.

Thanks for tuning in.

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect have a wonderful day.

Sure.

[music].

Okay.

Okay.

Okay.