Q3 2020 PTC Therapeutics Inc Earnings Call
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Unknown Executive: Ladies and gentlemen, today's conference is scheduled to begin shortly. Please continue to stand by, and thank you for your patience. (inaudible) Copyright 2020 Mooji Media Ltd. All Rights Reserved.
Unknown Executive: No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? Ladies and gentlemen, thank you for standing by, and welcome to PTC Therapeutics third quarter corporate update and financial results call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star then zero.
Lisa Hayes: I would now like to hand the conference over to your speaker, Ms. Lisa Hayes, Vice President of Investor Relations. Please go ahead, ma'am. Good afternoon. Thank you for joining us to discuss the PTC Therapeutics third quarter 2020 corporate update and financial results. Joining me on today's call is our Chief Executive Officer, Stuart Peltz, our Chief Financial Officer, Emily Hill, our Chief Development Officer, Matthew Klein, and our Chief Business Officer, Eric Pauwels. Before we start, let me remind you that today's call will include forward-looking statements based on current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements as any and all such risks can materially and adversely affect our business and results of operations.
Lisa Hayes: For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report, Form 10-Q, and annual report, Form 10-K, filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP financial measures is available in today's earnings release.
[music].
Ladies and gentlemen, thank you for standing by and welcome to PTC Therapeutics third quarter corporate update and financial results call. At this time, all participants are in a listen only mode.
After the speaker presentation, there will be a question and answer session.
Stuart Peltz: With that said, let me pass the call over to our CEO, Stupak. Thanks, Lisa. And thank you for joining us on the call. We have made significant progress this quarter with our R&D pipeline, as well as our commercial business, showing continued growth. We built PTC to create value for all stakeholders by discovering and developing novel therapeutics for patients with high medical needs and creating revenue by bringing these products to patients through our global commercial network. Our strong cash position allows us to continue to deliver on the promise of our pipeline to bring more therapies to patients and to grow the company. Let me go through some of the achievements this quarter.
To ask a question during the session you will need to press star one on your telephone.
Please be advised that today's conference maybe recorded.
If you require any further assistance. Please press Star then zero I.
I would now like to hand, the conference over to your Speaker Ms., Lisa Hayes, Vice President of Investor Relations. Please go ahead ma'am.
Good afternoon. Thank you for joining us to discuss the PTC or PTC therapeutics third quarter 2020, corporate update and financial results.
Joining me on today's call is our Chief Executive Officer, Stuart Peltz, Our Chief Financial Officer, Emily Hill, Our Chief Development Officer, Matthew Cline, and our Chief Business Officer, Eric Hello.
Stuart Peltz: Starting with RISD for the treatment of SMA, we are very excited about the strong launch of RISD in the U.S., not only for its efficacy and safety profile but also its convenience as the first at-home, orally-administered treatment for SMA patients two months and older. The ease of administration and access to a home-delivered therapy are particularly important to patients, especially during the COVID-19 pande A RISD showed clinically meaningful improvements in motor function and developmental milestone achievement across a broad range of ages and functional abilities of FMA patients.
Before we start let me remind you that today's call will include forward looking statements based on current expectations.
Please take a moment to review this slide posted on our Investor Relations website in conjunction with the call which contains our forward looking statements.
Our actual results could materially differ from these forward looking statements as any and such risks can materially and adversely affect our business and results of operation.
For a detailed description of applicable risks and uncertainties. We encourage you to review the Companys. Most recent quarterly report form 10-Q, and annual report form 10-K filed with the Securities and Exchange Commission as well as the company's other FCC filing we will disclose certain non-GAAP information during this call and for.
Commission regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP is available in todays earnings release with that let me pass the call over to our CEO stupid.
Stuart Peltz: The ABRISTI launch has had a very positive response from physicians, payers, and the whole SMA community. As a reminder, there is a high level of medical need in the SMA community with patients who are treatment-naive and patients who have concerns with durability or the administration burden of current therapy. Our partner Roche has reported that two-thirds of initial patients on the RISD were previously treated with Penrosa or Slogenza. We are seeing uptake across all types of SMA patients to date. 25% of patients
Thanks Lisa.
Thank you for joining us.
Joining the call today.
Significant progress this quarter with our R&D pipeline as well as our commercial business. So we continue to grow.
[laughter] to create value for all stakeholders like discovering and developing novel therapeutics for patients with our medical need including revenue board, bringing these products to patients through our global commercial and sure.
Our strong cash position allows us to.
Revenue to deliver on the promise of a pipeline to bring more therapies to patients and to grow further the company.
Stuart Peltz: Treated have been Type 1, with the remaining 75% being Type 2 and 3. There continues to be excellent progress in bringing EVRISD to SMA patients globally, with approvals already obtained in Brazil, Ukraine, and Chile. In addition, an NDA for EVRISD was filed in Japan, which triggered a 7.5 million milestone. RISD is also under review with the EMA, with a decision expected in April 2021. We appreciate the strong effort made by our partner, ROAD.
Let me go through some of the achievements this quarter.
Starting with the rooster for the treatment of wet summer, we're very excited about the strong long simple <unk> in.
The U.S. now going forward.
Good safety profile, but also.
First oh orally administered treatment.
For my patients two months old.
Use of administration and access to at home deliberate therapy.
Hercules important for patients, especially during the COVID-19 times Dumber.
Stuart Peltz: Let me comment on our commercial team's progress this quarter. Across our commercial portfolio, we saw increased patient uptake and associated revenue. Our net revenue increased 66% year over year, and net product revenue increased 16%.
Recently showed clinically meaningful improvements in motor function and developmental milestone achievement across a broad range of ages and functional ability of that for many patients.
The risks to launch has had a very positive response from.
Stuart Peltz: We're very pleased that we've continued to grow globally despite the COVID-19 challenges, including securing a purchase agreement with Brazil's Ministry of Health for translarnia. You can see we've made considerable progress with our commercial products, but I'm equally excited about the progress we've made in R&D programs and the value they will create. Let's start with our splicing plan. PTC was a pioneer in discovering and developing a selective small molecule. Splicing was the first product approved from this platform.
Position, payors and the whole or somebody can be.
As a reminder, there was higher but medical need in the or somebody can you with patients who are treatment naive patients who are concerned.
The ability or the administration burden of current therapies or.
Partner Roche has reported that two thirds of the initial patient on the wrist were previously treated with Spinraza So sensible.
We are seeing uptake across all types of this that many patients to date.
25% of patients treated hub in type one with the remaining 75% are type two absolutely.
Stuart Peltz: We have a number of exciting polio and splicing programs that are moving forward. Our plan is to create value by internally developing these products and bringing them to patients globally. After RISD, the next most advanced compound from our splicing platform is PTC 518, which is being developed for hunch. I'm excited to report that PQC 518 will enter the clinic this quarter, analogous to how we discovered RISD. PTC 518 was constructed to be an orally bioavailable molecule that distributes to all tissues in the body. It's very effective in crossing the blood-brain barrier and is highly selective. We've learned that these elements of selectivity, biodistribution, and pharmaceutical properties are critical to successfully developing differentiated splicing knowledge.
There continues to be excellent progress in bringing a roof definitely think since globally with a possible already obtained in Brazil, Ukraine in Chile. In addition in India for Ruth.
While the Japan.
Triggered the 7.5 billion milestone payment to be.
You see a.
Rusty is also under review with the Yemen with a decision expected in April 2021 real.
We appreciate the strong enough for me.
Gartner wrong.
Let me comment on our commercial teams progress this quarter across our commercial portfolio. We saw increased patient uptake and associated revenue, our net revenue increased 66% year over year and not net product revenue increased 16%.
We're very pleased that we've continued to grow globally, despite the corporate Nike challenges.
Already securing a purchase agreement with Brazil Ministry, Oh Retrans line.
Stuart Peltz: The Phase 1 trial will be performed in healthy volunteers, with results expected in the first half of the month, similar to the SMA program. And because there was a direct correlation between blood and brain levels in preclinical studies, the results from the Phase 1 Healthy Volunteer Study should allow us to demonstrate targeted engagement and proof of concept of the reduction of HTTMR. This will allow us to select doses for the subsequent study in HD patients. Now let me turn attention to our late-stage clinical program from our BioE plan. We recently announced that enrollment began in a registration-directed trial called MITEI with our compound Vatiquinone to treat mitochondrial epilepsy. As a reminder, about half of all children with inherited mitochondrial disease suffer from refractory seizures. These seizures result from dysregulation of the electron transfer process, leading to oxidative stress and inflammation.
[laughter], we've made considerable progress on our commercial products, but I'm really excited about the progress we've made in R&D programs and the value they will create.
I'll start with our splicing platform.
We did see was the party, we are discovering and developing a selective small molecule.
With the risk because the first profit improved from this platform.
We have a number of exciting wholly old legacy programs that are moving forward. Our plan is to create value for our newly developed these products and to bring them to patients globally.
Dr roof.
Next most advanced telephone for most flaky platform is did you see part one would you deem developed for Huntington's disease.
Excited to report that PTC part when they went to the clinic this quarter.
Now we do so how we discovered the route.
5.8 was constructed to be an orally bio available molecule that distribute all tissues in the body is very effective and crossing the blood brain barrier area and is highly selective.
Lord but these I would like to have a D bio distribution and pharmaceutical properties are critical to successfully developing differentiated splicing molecule.
Stuart Peltz: Reticulonone targets the enzyme 15-lipoxygen, which is a key regulator of the neural inflammation and oxidative stress response. We estimate that there are approximately 12,000 commercially addressable mitochondrial epilepsy patients globally. An additional registration-directed trial with Vatiquinone and Frederic Ataxia called MOVE-A is also planned to initiate by YARA. FA disease pathology results from high levels of oxidative stress, inducing neural inflammation, which is known to be an important FA disease pathology and progression.
Phase one trial will be performed in healthy volunteers with results expected in the first half of next year similar to the SMB program and because there was a direct correlation of blogging brain levels in preclinical studies the results from the phase one healthy volunteer study should allow us to demonstrate.
Marketing engagement and proof of concept of the reduction though H.T.M. on this.
This will allow us to flex doses for the subsequent study in HCV patients.
Now, let me turn the attention to our late stage clinical programs.
From our buyer platform, we recently announced that enrollment again, you know registration directed trial called my with our compounds that took one though.
Unknown Executive: Ritiquinone modulates these pathways to reduce inflammation. Previous Phase 2 results show that tritiquinone alters the course of FA disease, and we are excited to initiate the registration-directed study this year. Our third late-stage program is PTC 923 for the treatment of PKU, and we expect to initiate a pivotal phase 3 study in mid-2021. With an estimated 20,000 PKU patients in the U.S. alone, there continues to be high medical needs as the majority do not initially respond or are not adequately controlled on Kuvex. Results from previous studies demonstrated that approximately 50% more patients responded to PTC-923 when compared to Coovac. Furthermore, in these studies, the results demonstrated that the drug had greater than twice the reduction in phenylalanine levels compared to Coovac.
Wanted congeal epilepsy.
As a reminder, about half of all children with inherited Mike Mark mitochondrial disease suffer from refractory seizures.
These seizures result result from this regulation of the electronic transfer process, leading to oxidative stress them inflammation. We took were no targets the enzyme fiftyml packaging, which.
Which is the key regulator of the neural inflammation and oxidative stress response.
Estimate after approximately 12000 commercially addressable motor control epilepsy patients globally.
In addition, a registration directed study trial, which we took were known to Frederic utter a movie is also plan to initiate by year end.
Hey disease pathology results from high levels of Lucky strike.
Unknown Executive: We are currently conducting non-clinical studies to support the long-term dosing for the Plan Phase III trial. I want to turn now to the Trans-Latinx Interference Study, Study 045. You may recall that this was the outcome of our discussion with the FDA about potentially securing an accelerated approval for TransLarna in the U.S. so that these patients would be able to receive the therapy. I'm very happy to report that, with a very strong effort by the team, despite the challenges of COVID-19, the final muscle biopsy from the patient in study 045 has just been completed.
Interesting neuro inflammation, which is known to be an important epic disease pathology and progression.
We took were known molecules. They do these pathways to reduce inflammation.
Its phase two results showed that you took went on ultimately of course about the disease and we are excited to initiate a registration directed study this year.
Our third late stage programs is PTC 93 for the treatment of PK, you, where we expect to initiate a pivotal phase three study in mid 2021.
With an estimated 20000 PK you patients in the U.S. alone there continues to be our medical need as the majority did not initially respond or not to have it.
Unknown Executive: Preparation and analysis of the samples according to our protocol is now underway, and we look forward to sharing top-line data in the first quarter of 2021. We are excited that PTC has the potential to accelerate access to TransLara for U.S. patients. We are also continuing to make progress with our gene therapy plan. The Gene Therapy Manufacturing Facility in Hopewell is occupied and ready for production. As we have discussed previously, our most advanced program is the TREAT-AATC deficiency, where Dr. Singh has observed transformational and durable results in AADC deficient patients that have been treated for almost a decade. Our MAA has been submitted and is under review by the CHMP.
So on Qubec.
Results from previous studies demonstrated that approximately 50% more patients responded to PTC Nike three when compared to Qubec. Furthermore, These studies the results demonstrated that the drug at greater than twice the reduction in central Allenby levels compared to Qubec.
We are currently conducting nonpolitical studies to support the long term dosing for the planned phase three trial.
I want to turn now to friends long, they're just different study study all four or five.
You may recall that this was the outcome of our discussions with the FDA about potentially securing an accelerated approval for translarna in the U.S. So that these patients will be able to receive the therapy.
I'm very happy to report that the very strong effort by the team despite the challenge of appropriate 19th.
Unknown Executive: Due to COVID-19-related delays, PTC now expects the CHMP final opinion for the AADC deficiency application in the first half of 2021. For the BLA, PTC expects submission to the FDA will also be in the first half of 2021. We have recently initiated a Phase II-III trial for PTC299 for COVID-19 called FITE-19. We recognize that PTC299 has a unique dual mechanism that is potentially effective against both stages of the viral infection, including viral replication and enhanced immune response. The combination of the mechanism, the preclinical data, the well-established safety profile, and the compound's oral bioavailability gives us great confidence in PTC299's potential as a treatment for COVID-19. We anticipate reporting top-line results in the first half of 2021. With that... I'll now turn the call over to Matt Klein for key updates on our clinical program. Matt?
Final muscle biopsy from the patient study Oh poor five has just been completed.
Preparation and analysis on the samples according to our protocol is.
Now underway and we look forward to sharing top line data in the first quarter 2021.
Were excited that PTC has the potential to accelerate access translarna for U.S. page.
We are also continuing to make progress with our gene therapy platform. The gene therapy manufacturing facility and what was occupied is ready for production.
As we have discussed previously our most advanced program is a treat HCC deficiency, where we have observed transformational a durable result made you see deficient patients that had been treated for almost a decade.
Our Emergard has been submitted and under review by the sea It jumpy.
Due to COVID-19 related delays did you see now expects the Sears or be final opinion for agency. The person three application in the first half with 2021.
Matthew Klein: Thank you, Stu. We have had a very productive quarter as we continue to advance innovative therapies from all of our R&D platforms. Our development teams have been working tirelessly throughout this COVID-19 pandemic to minimize impact on ongoing trials and ensure that our next set of trials initiates without delay. As Stu mentioned, we are very excited to report that we have now completed the final muscle biopsies for Study 045, the translarmid. Analysis of the biopsy samples is now underway, and in accordance with the protocol, we remain blinded to study results until all biopsy analyses are completed
Billy PTC PTC expect submission to the FDA will also be in the first half its 121.
We also recently initiated a phase three trial for PTC Tonight not Rick.
COVID-19 Coke fight 90.
Recognize that because you do not have a unique dual mechanism that's potentially effective against both stages of the viral infection.
Viral replication and instantly response.
The combination of the mechanism the preclinical data the well established safety profile and the compounds oral bioavailability gives us great confidence in PTC two nights potential.
Treatment for coping Nike we.
We anticipate reporting top line results in the first half of 2021 with that.
Matthew Klein: As a reminder, the primary outcome of this study is an increase in dystrophin expression over baseline, as assessed by an electrochemiluminescence assay that we developed in collaboration with the FDA. We expect to have top-line data from the 045 district in study in Q1 2020. Turning to our BioE platform, we have initiated enrollment in the MI-V trial, the registration-directed trial of the tiquinone in children with mitochondrial epilepsy. This Phase 2-3 trial will enroll approximately 60 children with genetically confirmed mitochondrial and Associated Refractories.
I'll now turn the call the call over to Matt Klein for key updates on our clinical programs Matt.
Thank you Sir do you have had a very productive quarter as we continue to advance innovative therapies and all of our R&D plans.
Well the teams have been working tirelessly throughout this COVID-19 candidates to minimize impacts on ongoing trials and ensure that our next set of trials initiates without delay.
As Steve mentioned, we are very excited to report that we have now completed the final muscle biopsies for study whereby the translarna dystrophin stuff.
Analysis of the biopsy sample is now underway and in accordance with the protocol. We remain blinded to study results until all biopsy analyses are complete.
Matthew Klein: The study design includes a one-month run-in period to ensure that all eligible subjects have a minimum number of seizures, followed by a six-month parallel arm phase in which subjects will receive either vitiquinone or a placebo. The primary outcome of the trial is reduction in observed motor seizures, with secondary outcomes related to other aspects of seizure burden, as well as disease morbidity. The FDA has granted Tiquinone orphan designation and rare pediatric designation for the treatment of mitochondrial epilepsy.
As a reminder, the primary outcome of this study is it increasing dystrophin expression over baseline as assessed by an electrochemical luminescence asset that we developed in collaboration with the FDA.
We expect to have top line data from the over five district in starting in Q1 2021.
Turning to our buyer we thought we have initiated enrollment in the Mighty trough. The registration directed trial, particularly now in children with mitochondrial epilepsy.
Matthew Klein: The Phase 3 Vatiquinone-Predicataxone Trial, MOVE-FA, remains on schedule to initiate enrollment by year end. This trial will enroll approximately 110 children and young adults with phrasal catastrophic disorder. The study design includes an 18-month parallel-arm placebo-controlled phase, during which subjects will receive either tiquinone or a placebo. The primary endpoint measurement for this study is the Modified Fregio-Cataxia Rating Scale, or mTHRN.
Its phase two three trial will enroll approximately 60 children with genetically confirmed mitochondrial disease and associated refractory seizures that.
The study design includes a one one front in period to ensure that all eligible subjects have a minimum number of seizures, followed by a six month parallel arm phase in which subjects will receive either particularly known or placebo.
The primary outcome of the trial is reduction in observed motor seizures with secondary outcomes related to other aspects of seizure burden as well as disease Harbin.
Yes, he has granted particularly now in orphan designation rare pediatric designation for the treatment of mitochondrial epilepsy.
Matthew Klein: Key Secondary Endpoints Assessing Ambulation and Activities of Daily Life This endpoint strategy was developed in collaboration with both the FDA and. There are approximately 25,000 patients worldwide with pediatric cancer. With the second compound from our BioE platform, PTC 857, we have completed the Phase I Single Ascending Dose Study as planned, and expect to complete dosing in the MAD Study by year-end 2021. Now, turning to our spiky.
The phase three particularly don't reject the taxing trial move FSP remains on schedule to initiate enrollment by year end. This trial will enroll approximately 110 children and young adults, which we had tax.
The study design includes an 18 month parallel arm placebo controlled phase during which subjects will receive either particularly now where placebo.
Primary endpoint measuring for this study is the modified free chicken taxi rating scale for employers with key secondary endpoints assessing ambulation and activities of daily living.
Endpoints strategy was developed in collaboration with both the FDA and yes.
Matthew Klein: The PTC 518 Huntington Disease Program remains on schedule with a phase one trial and healthy volunteers to initiate this course. This phase One study includes both single and multiple ascending dose regimens to inform safety and pharmacologic parameters, as well as to guide dose selection for subsequent registration. Importantly, we are also planning to measure HTT mRNA levels in healthy volunteers to gain early proof of the splicing mechanism, as was done in the RISDAPlan SMA development program.
Yes, approximately 25000 patients worldwide, which featured the tax.
And the second compound from Abawi platform PTC five seven we have completed the phase one single ascending dose study as planned.
We expect to complete dosing to me and a deep study by year end 2012.
Turning to our splicing platform the PTC five wanting Huntington disease program remains on schedule with the phase one trial in healthy volunteers to initiate can this quarter yes.
This phase one study include both single and multiple ascending dose regimens to inform safety and pharmacologic parameters as well as Dick I don't selection for subsequent registration trials.
Matthew Klein: We expect to have data from the Phase 1 PTC 518 study in the first half of 2021. Next, I'll provide an update on our PTC 923 PKU study. We have initiated the long-term toxicology studies needed to support the initiation of the Phase 3 PKU trial that is scheduled to begin in mid-2021. This registration-directed trial will be a double-blind placebo-controlled study that will include both children and adults with PKU. PTC 923 is an oral formulation of synthetic sepia tarot. High Bioavailable Precursor to BH4, the Critical Co-Factor for Phenylalanine Hydroxyl, the Enzyme That Is Affected in People
Importantly, we are also planning to measure H.T. Ki m. R&D levels in healthy volunteers to gain early proof of slicing mechanism as it has done in there is the plant SMB development program.
We expect to have data from the phase one PTC 5.8 studies in the first half of 2020.
Next I'll provide an update on our PTC nicely free Pizza, Inc.
We have initiated long term toxicology studies needed to support the initiation of the phase. The PK you trial that is scheduled to begin in May 20 Twond.
Its registration directed trial will be a double blind placebo controlled study that will include both children and adults at Teekay you.
TC 93 is an oral formulation of synthetic seppi care.
Highly bio available precursor to be age for the critical factor for Fenway Onea hydroxyl the enzyme that is effective in T.K. you.
Matthew Klein: There are an estimated 50,000 PKU patients globally and 20,000 patients in the U.S. And, as Stu mentioned, there remains a significant unmet medical need for PKU. Now, turning to our gene therapy. Due to COVID-19-related delays, PTC expects the final CHMP opinion on the AEDC MAA in the first half of 2021, Treatment Procedures for AADT Deficiency Patients with the Commercial Time Lift to be completed by year-end 2020, and the submission of the BLA to the FDA in the first half of 2020. Finally, I want to provide an update on our FITE-19 trial, the study of PTC-299, our orally bioavailable DHODH inhibitor being developed for the treatment of COVID-19. Through its actions at DHODH, PTC-299 targets both key aspects of COVID-19.
There are an estimated 50000 PK you patients globally and 20000 patients in the U.S. and as Steve mentioned, there remains a significant unmet medical need for PK in patients.
Turning to our gene therapy platform due to COVID-19 related killings PTC expects the final teach him here.
Opinion on the AIDC anywhere in the first half of 2021, the treatment procedures to the agency deficiency patients for the commercial case to be completed by year end 2012.
The submission of the BIA late for the FDA to be in the first half of 2021.
Finally, I want to provide an update on our lighting trial. The study at PTC to nine now are orally Bioavailable D. H IDH inhibitor being developed for the treatment of Kobe 19th.
Its action to DHL gauge PTC to nine nine targets, both key aspects of coping Nike.
Matthew Klein: Viral Replication and the Cytokine Storm Leading to Lung Disease. The trial consists of two stages, with a planned interim analysis focused on safety at the completion of. Enrollment is ongoing and will remain on schedule to complete the first stage of the trial by year end and the second stage in H1 2020. I'll now pass the call over to Eric to provide a commercial. Thanks, Matt.
Viral replication and the cytokine storm, leaving to lung disease. The trial consists of two stages with a planned interim analysis focused on safety at the completion of stage one.
Enrollment is ongoing and remain on schedule to complete the first stage of the trial by year end and the second stage in each 120 21.
I'll now pass the call over to Eric provide a commercial.
Thanks, Matt.
Eric Pauwels: Our customer facing team at PTC delivered a strong quarter across the franchise with 16% growth year over year from our inline commercial product. We continue to accelerate growth with IMPLOD. Product revenues increased 68% year over year.
Our customer facing team at PTC delivered a strong quarter across the franchise with 16% growth year over year from our inline commercial products.
We continue to accelerate growth within plaza product revenues increased 68% year over year, and we continue to see newly prescribed patients.
Eric Pauwels: And we continue to see newly prescribed patients and reductions in time from prescription to commercial reimbursed therapy. Also, some U.S. payers have lessened access restrictions to emplaza therapy. And importantly, the current base of DMD patients has maintained high compliance with few patient discontinuations, demonstrating the long-term therapeutic benefits of emphylase. We continue bringing awareness to this importance of MPLAZA as the standard of care for all DMD patients with compelling real-world evidence. Demonstrating clinical benefit over, TransVarna continues to exceed our expectations in all regions outside of Brazil, where we were impacted by the timing of a group purchase We are pleased that, in October, we entered into a purchase agreement with Brazil's Ministry of Health to supply TransLarna to both new and existing patients.
Again, the reductions of time from prescription to commercial reimbursed therapy.
Also some U.S. pairs of lessened access restrictions to 'em Plaza therapy.
And importantly, the current state of DMD patients have maintained high compliance with few patient discontinuations demonstrating the long term therapeutic benefits have been plaza.
We continue bringing awareness to this important each of them Plaza as the standard of care for all DMD patients with compelling real world evidence demonstrating clinical benefit over pretty bizarre.
Trends, Florida continues to exceed our expectations in all regions outside of Brazil, where we were impacted by the timing of a good purchase order in Brazil in Q3.
We are pleased that in October we entered in a purchase agreement with Brazil's Ministry of health to supply Translarna for both new and existing patients.
Eric Pauwels: The PTC Brazil team, DMD advocacy groups, and key opinion leaders all worked together to bring awareness of this important therapy, and we were ultimately successful in securing the order with Brazil's Minister of Health and ensuring continuity of treatment for DMD patients. This order is important given the governmental administrative delays in Brazil, which was hit exceptionally hard by the pandemic. The agreement specifies two shipments, one of which was received this quarter, and the subsequent one is expected in the first half of 2021. Now I'm switching to text settings.
The PTC, Brazil team DMD advocacy groups.
And the key opinion leaders all work together to bring awareness of this important therapy.
And we were ultimately successful in securing the order.
With Brazil's Ministry of Health.
And ensuring continuity of treatment for DMD patients.
This order is important given the governmental administrative delays in Brazil hit exceptionally hard by became demick.
The agreement specifies two shipments one of which was received this quarter and the subsequent one is expected in the first half of 2021.
Now switching to tech savvy.
Eric Pauwels: We continue to engage in pricing discussions for TecCeti in Brazil and expect to finalize the public price by the end of the year. For both TxETI and WeLibre, we continue to engage in patient recruitment in Latin America and continue to see success in these programs. We also continue to engage in early access programs in Latin America as we await a decision on our waiver and visa filing in Brazil. Now, moving on to AADC.
We continue to engage in pricing discussions for tech savvy in Brazil, and expect to finalize the public price by the end of the year.
For both typesetting anyway, Libra, we continue to engage in patient finding in Latin America I continue to see success in these programs.
We also continue to engage in early access programs in Latin America, as we await a decision on our white Libra and diesel filing in Brazil.
Now moving on to agency.
Eric Pauwels: We continue to aggressively pursue patient-finding activities in preparation for potential launches in Europe next year. We have expanded our geographical reach to more than 17 countries and have implemented 60 screening programs focused on enriched high-risk populations, particularly in cerebral palsy and epilepsy clinics. New programs such as PTC Pinpoint have been launched, which is a single source that health care providers can access to screen potential AADC patients via targeted genetic panels at no cost. We are also adapting to local country needs by leveraging local diagnostic labs in key markets.
We continue to aggressively pursue patient finding activities in preparation for potential launches in Europe next year.
We expanded our geographical reach in more than 17 countries and have implemented 60 screening programs focused on enriched highwoods population, particularly in cerebral palsy and epilepsy clinics.
New programs, such as PTC, pinpoint where launched which is a single source that health care providers can access to screen potential AIDC patient via targeted genetic panels at no cost.
We were also adapting to local country needs by leveraging the local diagnostic labs in key markets and lastly, we are partnering with key centers of excellence globally to develop algorithms to execute patient fighting against existing high risk patient databases.
Eric Pauwels: And lastly, we are partnering with key centers of excellence globally to develop algorithms to execute patient findings against existing high-risk patient databases. We are also actively working with these key treatment centers to ensure that they are ready to treat AADC patients. In addition, we accelerated our digital presence with health care professionals through the continued virtual masterclasses and for patient advocacy by supporting AADC Awareness Day and the great informational content at aadcfamilynetwork.com. These initiatives have proven useful in education and awareness about AADC and support earlier diagnosis of patients. I will now turn the call over to Eric. PTC continues to deliver strong growth in our business while maintaining a robust balance.
We are also actively working with these key treatment centers to ensure that they are ready to treat HCC patients.
In addition, we accelerated our digital presence with health care professionals through the continued virtual master classes and for patient advocacy by supporting a DC awareness day and the great informational content.
At a DC family network Dot com. These.
These initiatives have proven useful in education and awareness about ADCC and support earlier diagnosis of patients.
Now I'll turn the call over to Emily.
Thanks, Eric PTC continues to deliver strong growth in our business, while maintaining a robust balance sheet.
Unknown Executive: As Stu shared, we are very pleased with the multiple international approvals of F-RISB and the start of a strong launch. In the third quarter, we received a total of $35 million in milestones, including the first commercial sale in the U.S. and the filing of the MAA with the EMA. Additionally, in the fourth quarter, we received $7.5 million from Roche for the SMA Japan submission. On October 15th, Roche reported initial Evers D sales of approximately 8 million Swiss francs. As a reminder, PTC retains approximately 57% of Ed Frisbee royalties until Royalty Farmer receives a return of $1.3 billion, after which 100% of the royalties revert to PTC.
As Steve shared we are very pleased with the multiple international approvals that front feet on the start of a strong launch.
In the third quarter, we received a total of 35 million and milestones with the first commercial sale in the U.S.
And the filing of the M&A with email.
Additionally, in the fourth quarter, we received 7.5 million from Roche for that to me Japan submission.
On October 15th Roche reported initial ever see sales of approximately 8 million Swiss francs.
As a reminder, PTC retains approximately 57% of the upfront royalties until royalty pharma receives a return of 1.3 billion after which 100% of the royalties revert to PTC.
I'll now highlight for third quarter 2020 financial results, which are summarized in the press release issued earlier today start.
Unknown Executive: I'll now highlight the third quarter 2020 financial results, which are summarized in the press release issued earlier today. Starting with our top-line results, we reported $118.4 million in total revenues in the third quarter of 2020, a 66% increase year-over-year. The $118.4 million includes $82.7 million of net product revenue and $35.7 million of collaboration and royalty revenue.
Starting with our top line results, we reported 118.4 million and total revenues in the third quarter up 2020, 66% increase year over year the.
The 118.4 million includes 82.7 million of net product revenue and 35.7 million of collaboration and royalty revenue.
Unknown Executive: TransLarna continued to show growth with the exception of the delay in the timing of the Brazil order for TransLarna, and we are pleased that we have now secured that order. As Eric mentioned, the first segment of the order was received in the fourth quarter. TransLarna Net Product Revenues were $43.4 million for the quarter, compared to $48.3 million in the third quarter of 2019.
Plaza on Translarna continued to show growth with exception of the delay in timing of the Brazil like her for Translarna and we are pleased that we have now secured that'll occur as Eric mentioned, the first segment of the order was received in the fourth quarter.
Translarna net product revenue is for 43.4 million for the quarter compared to 48.3 million in the third quarter of 2019 again, the delay of the person who purchase order is the primary driver of this year over year decrease Translarna continues to exceed our expectations outside of Brazil, and we are seeing continued global growth.
Unknown Executive: Again, the delay of the Brazil Group purchase order is the primary driver of this year-over-year decrease. TransLarna continues to exceed our expectations outside of Brazil, and we are seeing continued global growth. From PLAZA, we reported net product revenues of $38.5 million for the third quarter of 2020 compared to $22.9 million reported for the third quarter of 2019. Growth in net product sales was driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business. Non-GAAP R&D expenses were $83.8 million for the third quarter of 2020, excluding $9.2 million in non-cash stock-based compensation expense, compared to $58.1 million for the third quarter of 2019, excluding $5 million in non-cash stock-based compensation. This year-over-year increase in R&D expenses reflects costs associated with advancing the gene therapy and BioE platforms, increased investment in research programs, and advancement of the clinical
From Plaza, we reported net product revenue was up 38.5 million for the third quarter of 2020 compared to 22.9 million reported for the third quarter up 29 Pete.
Growth in that product sales were driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business.
Non-GAAP R&D expenses were 83.8 million for the third quarter of 2020, excluding 9.2 million and non cash stock based compensation expense.
Care to 58.1 million present third quarter 2019, excluding 5 million and non cash stock based compensation expense.
This year over year increase in R&D expenses reflects cost associated with advancing the gene therapy and Biovance platforms increased investment in research programs and advancement of the clinical pipeline.
Unknown Executive: Non-GAAP ST&A expenses were $50.2 million for the third quarter of 2020, excluding $7.6 million in non-cash stock-based compensation expenses, compared to $43.8 million for the third quarter of 2019, excluding $5.5 million in non-cash stock-based compensation. The increase in SG&A was due to continued investment in our commercial activities and manufacturing operations to expand our portfolio. A net loss of $69.7 million for the third quarter of 2020 compared to a net loss of $60 million for the third quarter of 2019. Cash, cash equivalents, and marketable securities totaled approximately $1.14 billion as of September 30, 2020, compared to $686.6 million as of December 31, 2019.
Non-GAAP <unk> expenses were 50.2 million for the third quarter of 2020, excluding 7.6 million and non cash stock based compensation expense.
Compared to 43.8 million for the third quarter of 2019, excluding 5.5 million and noncash stock based compensation expense.
The increase in S. DNA was due to continued investment in our commercial activities and manufacturing operations to expand our portfolio.
Net loss was 69.7 million for the third quarter of 2020 compared to net loss of 60 million for the third quarter of 2019 cash.
Cash cash equivalents and marketable securities totaled approximately $1.14 billion at September Thirtyth 2020, compared to 686.6 million as of December 31st 2019.
Unknown Executive: The cash, cash equivalents, and marketable securities balance as of September 30th includes $650 million in cash received by PTC in July upon the closing of the Royalty Pharma Monetization Deal. I will now hand the call over to the operator to start the question and answer session. Operator, Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.
The cash cash equivalents and marketable securities balance as of September Thirtyth includes the 650 million in cash.
By PTC in July upon the closing of the royalty pharma monetization yeah.
I will now hand, the call over to the operator start the question and answer section.
Operator.
Thank you as a reminder to ask the question you need to press Star one on your telephone to withdraw your question press. The pound key please standby will be compelled to too many roster.
Operator: Please stand by while we compile the Q&A roster. Our first question comes from Eric Joseph with J.P. Morgan. Your line is open. Hi, good evening. Can you hear me?
Our first question comes from Eric Joseph with JP Morgan Your line is open.
Hi, Good evening could you hear me.
Yes.
Okay, great. Thanks.
Thanks for taking the questions.
Eric William Joseph: Yeah. Oh, great. Thanks for taking the questions. I just have a couple on PTC 518 for Huntington's, if I could. First, could you, I guess, with plans still being on track to start the Healthy Volunteer Study within this quarter, can you confirm that you filed the IND at this point? And I'm just also wondering, based on your dose ranging finding studies, what sense you have right now of sort of the starting dose, what the biologically effective dose might be in humans, and do you have a sense of how many dose cores you would anticipate escalating through Sure, maybe we'll start with the Huntington, right?
Hi, Thanks for taking the questions Dick I just had a couple on PTC five when April Huntingtons, if I could.
First could you I guess with plan the plan for being on track to.
Start to how they've gone to a city within this quarter can you confirm.
Does that mean that you filed the I. Indeed at this point and I'm. Just also wondering based on your dose ranging finding studies what sense you have right now sort of it starting.
What the biologically active dose might be in humans and do you have a sense of how many dose cohorts you would anticipate a escalating through in the phase one study.
Sure, maybe we'll start with the.
Huntington right. So we're actually pretty excited about this could be first in humans.
Unknown Executive: So we're actually pretty excited about this. It will be the first in humans where the Huntington protein, which is a splicing protein, a splicing molecule that reduces the level of both the Huntington messenger RNA and Huntington protein. And we've shown that it's, again, to remind you, it's an orally bioavailable molecule that passes the blood-brain barrier, stays within the brain, and very nicely reduces both the RNA and Huntington protein. And we've shown that the levels that we've observed in the blood are the levels that we see in the brain. And the levels of reduction in Huntington are what we see in the brain in preclinical models. So we feel pretty good that by being able to look at the PK and levels within the Healthy Volunteers, we'll be able to find the exposures that we want to get to within patients. And so we'll be doing the first in humans, and I'll let Matt talk a little bit about the Phase 1 study for PTC 518. Yes. Hi Matt, here.
In which the the hundreds of profit, which is a splicing protein splicing molecule.
It reduces.
The level of the both deer Hunter you too have nothing John <unk>.
Protein and we've shown that it's again to remind you it's an orally bio available molecule.
With that.
Oh passes the blood brain barrier, Oh stays within the brain and very nicely reduces both the army.
Protein.
And what's the sort of thought to back and we've shown.
That the levels that we've observed good luck.
Our oh the levels that we see in break this it will be and the levels of reduction in talking to them, what weve seen in bringing in preclinical model.
Model.
So we feel pretty good that by being able to to look at the P. Carey's levels within.
The healthy volunteers will be able to find the exposures that we want to get too.
Within.
With that patients and so we'll.
We'll be doing first in human and outlet.
Matt talk a little bit about.
The.
The phase one study for a bit stupid money.
Yes, so they're not here. So we are going to as we and as he said well be starting the phase one before the end of the year. We are conducting is ex U.S. So there was no 90 file but there was a CTO team that I can share that all of the regulatory and ethics documents that needed to be a crew cabin approved so we're just now getting to the starting blocks.
Matthew Klein: So we are going to, as we said, we'll be starting phase one before the end of the year. We are conducting this outside of the US, so there was not an IND file, but a CTA was obtained, and share that all of the regulatory and ethical documents that needed to be approved have been approved, so we're just now getting to the starting blocks to get the study going, having passed all of those regulatory hurdles. This will be, of course, the SAV and MAV study, and as we mentioned, we're excited about having this opportunity as well to get important proof-of-splicing mechanisms in the Phase I study of healthy volunteers, again, analogous to what we did with RISDAPlan and the SMA development. I got it.
The study going.
Having passed all of those regulatory hurdles and this will be of course, the FCC Internet savvy and as we mentioned we're excited about having this opportunity as well to get important sleepy spicy mechanism in a phase one study in healthy volunteers again analogous to what we did it with risk declared any estimate at all.
Got it.
Matthew Klein: And as far as tracking or collecting samples in the periphery to look at MRNA downregulation of Huntington, is that something you expect to be tracking as early as the single ascending dose portion, or would that happen more in the multiple ascending dose portion of the day?
As far as tracking are collecting samples in the periphery do you look at.
M&A down regulation of Huntington.
Is that something you expect to be tracking as early as I said the.
The single ascending dose portion or.
Will that happen more in that the multiple ascending dose dose.
Unknown Executive: Yeah, we'll be, you know, the nice thing about this is that you obviously see the changes. We'll look at, we'll be looking at both the essay and the multi-gov. And so then, obviously, what we'll do is we'll share the relevant data as it becomes available. Great.
Portion of the study.
Yeah, we'll be.
The nice thing about this but you obviously.
In June well.
Well look you will be looking both at the activity as well as the Multek goes until then.
Do is we'll share.
The relevant data.
As it becomes available.
Great. Thanks for taking the question.
Eric William Joseph: Thanks for taking the questions. Thank you. Our next question comes from Danielle Breaux. Raymond James, your line is open. Hi, guys. Good afternoon. Thanks so much for the questions. So I guess a couple.
Sure.
Our next question comes from Daniel Brims, Raymond James Your line is open.
Hi, guys. Good afternoon. Thanks, so much for the question so.
I guess a couple first I'd be curious to hear what your thoughts were on the scholar Roxy then estimate that were announced this week and do you have any thoughts on how that might ultimately a fit into that human landscape in the long term and then.
Unknown Executive: First, I'd be curious to hear what your thoughts were on the Scalarock data and SMA that were announced this week, and do you have any thoughts on how that might ultimately fit into the treatment landscape in the long term? And then a couple of follow-ups on your mitochondrial epilepsy trial. Sure, so when you're thinking about the underlying cause of the disease, like an SMA, the ERISA plan really treats the underlying cause, right? It increases the amount of SM protein, and that's, you know, actually quite important. And we've seen, obviously, that it helps SMA patients both gain developmental milestones and meaningful functional improvement in SMA types one, two, and three, so we think that's important. Now, when you think about other things that could be improved, in terms of, for the patient, that is, combination therapy that can help muscle growth and degeneration in concert with having the SMA protein, then, you know, combinations like that can be quite useful, as you could see improvements in muscle tone along with the SMA protein.
A couple of follow up on your macro kind of GL epilepsy trial.
Sure so the Uh huh.
You know obviously.
When you think about the.
The underlying causes of disease like in that so I'm married you know of Riverview resupply.
I haven't really treats the underlying cause of the produces the amount of protein and that's you know.
Actually quite important.
Seen obviously that helps us.
SMB patients.
Both game developer milestones.
Couple functional improvements in.
So many types one.
Right. So we think that's the portal no. When you think about other things that could be true in terms of for the patients that is that a combination therapies that can help muscle growth agenda. They should in concert with heavy that's number one.
Protein.
You know we come to me seems like that can be quite useful, but you could see.
Improvements in muscle tone that long long with.
Yeah from a perfect. So.
Unknown Executive: So, anything that can help patients, which, obviously, we are excited about, and that, you know, we and our partners are obviously thinking and considering what are the next steps in terms of what's the best decision for patients in terms of this program? Clearly, the notion of being a muscle is really quite important.
The team that can help patients. So obviously, we are excited about that you know we him apart our partners are obviously.
Acumen Conservative what are the next steps in terms of what's the best decision for the patients for this program.
Really.
The notion of a big muscle.
Unknown Executive: So, you know, we're excited about the notion that it's, you know, especially the type 2, 3 patients, that they can more rapidly show improvement, and it would be beneficial to have more power than have problems. Understandable. Thanks for that.
Is really quite important.
So we're excited about the notion that you know, especially the type two three places that they can more rapidly show improvement.
And if we would be profit to sell them a.
More power than having companies.
Understood. Thanks for that and then just now that the mitochondrial epilepsy trial is out up and enrolling do you have any any rough idea, but timelines might look like for enrollment and then can you provide a little more color I'm just remind us again.
Unknown Executive: And then, just now that the mitochondrial epilepsy trial is up and enrolling, do you have any rough idea of what timelines might look like for enrollment? And then, can you provide a little more color, just remind us as to what you saw in the expanded access program in terms of seizure benefits that gave you confidence in this indication? Thanks.
What you saw in the expanded access program in terms of future benefits that gave you confidence.
In this indication thanks.
Unknown Executive: Sure, so just to remind everybody, we're doing a mitochondrial epilepsy, a refractory epilepsy trial, and really, electron transfer and oxidative stress are key points in these refractory epilepsy patients. And so we have a unique inhibitor, a 15-lipoxygenase inhibitor, that is actually a key regulator in controlling oxidative stress and redox and neural inflammation. So we're pretty excited about that, and there's certainly data, there's certainly a preponderance of data showing that this is a key regulator. And so based on that, there's some early data that I'll have Matt talk about in terms of the data that we have with Tiquanone. So this is initiating, and we think that the mitotiamine epilepsy, we're standing any other additional delays that could Consequence of COVID could be completed by the end of 2022. So, Matt, you want to go through a little bit?
Sure So just to remind everybody.
Oh, we're doing autocam dual epilepsy refractory epilepsy.
Trial, when does that really be.
Ill, let sometimes for.
Occidental stress our key points with it.
These refractory epilepsy pigs and.
And so we have a unique inhibitor.
Will approximate inhibitor that is actually a key regulate it.
In controlling oxidative stress lots of neuro inflammation. So we're pretty excited about that was certainly a data there.
Certainly Oh, Oh preponderance of data showing that this is a key regulator and so based on that there was some early days with that I'll have Matt talk about Oh in terms of the data that we have with a particular node but.
But the money.
So this is initiating and we see that the mitochondria epilepsy.
No.
Extending maybe other additional delays that could be a consequence on cold it could be completed by the end of 2022.
So Matt you want to go through a little bit.
Matthew Klein: Yeah, absolutely. Danielle, thanks for the questions. As you mentioned, we're expecting data by the end of 2022, and what we're doing is working closely with foundations, physicians, and family networks throughout the world where we're going to have study sites to try and get the study enrolled, obviously, as quickly as possible. Also, in light of COVID, we've developed a strategy of really having globally distributed test sites so that we can be prepared to deal with what will be sort of the emergence of COVID in different areas over time.
Yes, absolutely yes.
Thanks for the question as you mentioned, we're expecting data by end 2022.
What we are doing is working closely with the foundations physician and failing networks throughout the world Gold study sites to try and get the study enrolled obviously as quickly as possible also in light of coated we developed a strategy of really having globally distributed sites. So that we can be prepared to deal with.
It will be sort of the emergence of covidien different areas over time. Finally, we've also been able to incorporate a number of different aspects into the protocol that will allow for a remote assessments again, so we ensure that isnt as minimum it's minimal impact as possible to the conduct of the study found some code. It this way if any that may arise.
Matthew Klein: And finally, we've also been able to incorporate a number of different aspects into the protocol that will allow for remote assessments. Again, so we ensure that there is as minimal impact as possible to the conduct of the study from COVID from this wave and any that may arise. Turning to the historical data, so we've looked at, obviously, 243 mitochondrial disease patients in a number of different studies over time in the Expanded Access Study, as well as some disease-specific or indication-specific studies. And what we've seen in a number of these different studies is an impact on seizures themselves and many aspects of seizure-related morbidity. So in Expanded Access, as you mentioned, we had reports of decreased seizure frequency, refractory status epilepticus. In trials of other mitochondrial disorders, such as Leaf Syndrome, where seizures occur, we have reports of decreased seizure frequency in these patients. And in a study of a specific mitochondrial disease subtype known as PCH-6, or constitutory hyperplasia type 6, which is mitochondrial epilepsy, seizures will start in the first days, weeks, or life, and these kids just basically continue to seize refractory to all medications and typically die from seizure-related complications in early childhood.
Turning to the historical data. So we looked at obviously spent 43 mitochondrial disease patients in a number of different studies over time, we expanded access studies as well as some see specific or indication specific studies and what we've seen in a number of these different studies isn't impact on seizures themselves and many aspects of seizure.
Your related morbidity ceramics in expanded access as you mentioned, we have reports it decreases your frequency resolution us refractory status epilepticus into.
In trials and other minor talking sort of such as leasing draw where caesars occur. We have reports a decrease of seizure frequency in these patients and in May.
Investigator study in a in a specific my time, you'll see subtype known as PC six across several hyperplasia type six which is a mitochondrial epilepsy seizures will start in the first eight weeks a light. These kids this basically continue to seize.
Refractory to all medications typically die procedure related complications early childhood.
Matthew Klein: We treated five subjects at a single site, and that study demonstrated a significant reduction in seizure frequency, in some cases, over 70 or 80 percent, as well as the ability to influence the occurrence of status epilepticus, and importantly, a significant reduction in seizure-related hospital days. So really, when we look at the collection of studies we've done, we're seeking evidence across many different mitochondrial disease subtypes of an impact not only on seizures themselves but, importantly, on seizure-related morbidity. Great Thanks so much, Matt, for all those details. I appreciate it. Our next question comes from Tazeen Ahmad with Baking America. Your line is open.
We treated five subjects at a single site in that study demonstrated a significant reduction in seizure frequency in some cases over 70 or 80% as well as the ability to influence the occurrence of status epilepticus and importantly, a significant reduction in seizure related hospital days, so really when we look over the collection of studies Youve done.
Seeking evidence across many different a lot of controversy subtypes of an impact not only on seizures that sells but importantly on seizure related morbidity.
Great. Thanks, so much not for profit as detailed appreciate it.
Our next question comes from to Xena models with Bank of America. Your line is open.
Tazeen Ahmad: Hi, good evening. Thanks for taking my questions. Sue, I wanted to get a little bit of color, if I could, about what our expectations should be for the TransLarna data. You know, how much dystrophin production do you think is needed? Have you had any preliminary discussions with the agency on this point? And if they do give you the go-ahead, can you talk us through the timelines for what would need to happen in order for you to get formal approval for the drug in the U.S.? And then I have a couple of follow-ups. Sure.
Hi, good evening, Thanks for taking my questions theme I wanted to get a little bit of color if I could about what our expectations should be for the translarna data.
You know how much dystrophin production do you think is needed have you had any preliminary discussions with the agency on this point and if they do give you. The go ahead can you talk us through timelines from what would need to happen in order for you to to get like a formal approval for the drug giving you.
Okay, and then I have a couple of follow up thanks.
Sure.
Unknown Executive: So we're, you know, obviously pretty excited that we were able to complete this trial and really get all 20 patients in so that we'll be able to generate the data. And so with the positive distribution data, this is what we've talked with the FDA about, that with the positive distribution data coupled with the really extensive clinical and safety data that we've accumulated on TransLarna, we'll move forward with a submission in the first half of the year. And you might recall, and we've talked about this multiple times over the years, that this trial was discussed with the FDA. The use of the ECO was discussed with them as well. And really, the result is if we could show a statistically significant increase in dystrophin levels over baseline, we expect that we'd be able to pursue an accelerated approval in the U.S. on this. So, we've now completed all the biopsies in accordance with the protocol, which we obviously remain blinded to until everything is analyzed and completed. So the, again, the timeline there. [inaudible] who I think have been waiting for some time.
So were you know obviously pretty excited that we were able to complete this trial wasn't really get all 28.
They should saving so that we'll be able to generate the data.
And so with the pot so with the positive distant from data. This is what we've talked with the delay on that with the positive dystrophin data coupled with the.
Really extensive clinical and safety data that we've accumulated on Translarna will.
Unknown Executive: Okay, and then a question on AADC. How is the patient identification process going for that indication? And can you give us a little bit of color on what the rate limiting factors are right now to get the BLA?
The rate limiting factors are right now is to get the BLE.
Tazeen Ahmad: Sure. So let's start with Eric. Why don't you actually go through a little bit of your work that you and your team have been doing on patient identification? Sure. Hi Tazeen.
Sure so.
So let's start with.
Oh, we feel like once you actually go through a little bit on the the you. Your work that you and your teams have been doing on these.
Patient identification.
Eric Pauwels: Right now, we're really actively working to identify patients, and obviously, we know this is an ultra-rare disease with approximately 5,000 patients worldwide. So we've actually increased the levels of patient education, and we've rolled out a number of things, including the master class program. And actually, the digital presence that we've had has attracted a tremendous amount of interest from healthcare providers. And what we've done more so in the last probably three or four months is expanded our geographical reach. We are now in more than 17 countries where we know we're going to have access and reimbursement, and we've implemented 60 screening programs that are really focused on the high-risk population, and particularly those cerebral palsy clinics.
Yes, you are right to be right and right now we're really actively working to.
Identified patient and obviously, there's only one.
This is an ultra rare disease with approximately 5000 patients worldwide, but we've actually increased the levels of patient education result out a number of things, including the Master class program and actually the digital presence that would have caused attracted a tremendous amount of interest from health care providers and what we've done and more so in the last probably three or.
For Barclays expanded our geographical reach now are in more than 17 countries, where we know we're going to have access in reimbursement.
And we've implemented 60 screening programs that are really focused on.
The high risk population, particularly low single travel policy clinics.
We launched a program called pit PCC pinpoint this quarter this last quarter and it's really a nice single source.
Eric Pauwels: We launched a program called PTC Pinpoint this quarter, this last quarter, and it's really a nice single source where healthcare providers can go right to and screen patients via this genetic-targeted panel, and there's really no cost. I think during the middle of COVID, we got a lot of tests out there, but there was some disruption in terms of patients being actually screened and tested and getting results back. This last quarter, I think we've seen a tremendous amount of movement, and we have really upped the numbers in terms of screening. So I think overall, it's going quite well. Are you about to give us an update on how many have actually been identified? I think you started that in the early stages.
Where healthcare providers can go right to screen patients. This via this genetic targeted well and there's really no cost I think during the middle of Covance. We did we got a lot of tests out there, but there was some disruption in terms of patients being actually screened and tested and getting results back.
This last quarter I think we've seen a tremendous amount of movement and we have a really up the numbers in terms of screening. So I think overall, it's going quite well.
And you are about to give us an update on how many have absolutely been identified I think you have started to.
Tazeen Ahmad: Well, we continue, we continue. I mean, our goal is to continue to have 300 or more addressable patients, and addressable obviously means patients that could be treated. And we are looking in those markets globally where we have access to, you know, high-cost rare disease medicines. And we want to have those patients ready to go by the time we have a first commercial launch. I think, you know, we're on track to continue to screen that high-risk, that sort of high-risk and enriched population. And more than anything else, we're becoming better and better at understanding which screening programs are giving us the best results. Okay, thanks. Our next question comes from Vincent Chin on Bernstein. Your line is open.
Early stages.
Well, we'll continue we continue I mean, our goal is to continue to have 300 or more addressable patients and addressable obviously means patients that can be treated and we are looking in those markets globally, where we have access to.
Hi cost rare disease medicines, and we want to we want to have those patients ready to go by the time, we have a first commercial launch.
I think we're on track to get to two continuing to screen that high.
That sort of high risk and enriched population and more than anything else, we are becoming better and better at understanding which screening programs are giving us the best results.
Okay. Thanks.
Our next question comes from Vincent Chen with Bernstein. Your line is open.
Unknown Attendee: Great. Thank you very much for taking my questions and congratulations on the progress. A couple of them, one on PTC 518 and then one on ADC gene therapy. So, starting with PTC 518, I was wondering if you could provide us with some additional color on this initial trial in healthy volunteers. Specifically, I'm kind of curious just what are the endpoints of the study beyond peripheral Huntington knockdown? What level of peripheral Huntington knockdown are you looking for, and how do you measure it? And I guess, just sort of timing wise, what's your current thinking for when you would have a readout to support moving into patients? Let's start with that one and then follow up on the next one on ADC.
Thank you very much for taking my questions and congrats on for I guess, a couple of them one on PTC 5.8, and then one on the AIDC gene therapy, So starting with PTC five when it I was wondering if you could provide us with some additional color on the this initial trial in healthy volunteers, specifically I'm kind of curious just what are the endpoints of the study beyond peripheral Huntington knockdown what level of peripheral.
You can knock down you're looking for and how do you measure isn't.
I guess just timing wise, what what's your current thinking for when you would have a readout to support moving into in divisions.
Let's talk about one and a follow up on it and then an excellent AIDC.
Yes sure.
Unknown Executive: Yes, sure. So, as you know, right, because we spent a lot of time making sure that it was selective and specific for Huntington's and that we could measure the Huntington's disease gene on and protein dominant in blood. And so in the volunteer study, obviously, we are looking at safety as well as looking at RNA and protein levels. We are escalating both single and multi-threaded doses, and we are looking for changes probably up to 50% in reduction. You might remember that in the preclinical trials. And this is again, a nice...
So is it right. So as you know right because it's.
We spent a lot of time with cancer other selective and specific.
For how many tools that we can measure.
The Huntington on protein dominant.
Blood and so in the volunteer study obviously.
Our city fees as well as looking in our name protein levels.
Escalating both single and multiple ascending dose and we're looking for changes probably up to 50%.
The reduction you might remember that in the preclinical trials and this is again a nice.
Unknown Executive: Aspect of having an orally bioavailable drug that you can measure In preclinical animal studies where we can look in both the blood and the brain, we're able to look at exposures of a small molecule in the blood and demonstrate really that it was almost a one-to-one correlation between what we saw in the blood versus what we saw in the brain. We looked at the reductions as a consequence of that, and so we were So we feel that we can, in a sense, dial it up or down depending on the level of the drug that we're shooting the exposure Protein And again, the other nice aspect of this is that because it's an orally bioavailable molecule, it gets into all Passes of the blood there. It gets to all the blood tissues of brain tissue, so you see the whole brain getting.
Aspect to happen the orally bioavailable drug thats going to measure.
In preclinical animal studies, where we can book in both Brooklyn brain, we are able to look at our exposures.
Exposures of a small molecule in the blog demonstrate really bad there was almost a one to one correlation soon what we saw in the glut versus what was really looked at the reductions as a consequence of that so we were able to see you know determine exposures.
That reduced pretty.
Pretty substantially the left from the Huntington's protein. So we feel that we can you know the sense dialing up or down depending on the level.
Drugs that were shooting up the exposure.
Reduce the level of protein.
And again the other nice aspect of this is because it's an orally bio available molecule it gets into all.
Super Bugs Viereck us all blood tissues, a brain tissues that are.
You see the whole grain getting it and so we can measure in all aspects of the brain and shows that we've gotten to everywhere. So what we'll be doing here.
Unknown Executive: And so we can measure in all aspects of the brain and show that it's gotten everywhere. And so what we'll be doing here is, you know, obviously measuring the exposure levels, looking at safety, and the reduction of the Huntington RNA and protein so that we can, you know, define an exposure of up to 50% of HPT. That's the, so really it's defining what we think is the right dose and looking at the, you know, the exposure and safety characteristics. And then maybe a second one on ADC gene therapy. So I guess you alluded to this delay in the CHMP.
Obviously measuring exposure levels looking like safety and the reduction, though the Huntington our native protein.
So that we can you know just to find an exposure of up to 50%.
A reduction of HDTV. That's the so really this is the finding what we think the right dose.
And Lumpiness or you know the exposure and safety characteristics.
I see and then maybe a second one on the AIDC gene therapy. So I guess you Lucy this delay in the DCH MDM measures related to sort of a covert and just taking a little longer to respond to whatever questions. I was hoping you could provide a little color on the questions from the Mi and how they compare to what the FDA has.
Matthew Klein: I imagine it's related to some sort of COVID and just taking a little longer to respond to the letter of questions. I was wondering if you could provide a little color on the questions from the EMA and how they compare to what the FDA has asked for. And then just to sort of zero in a little bit on the timeline, could you confirm if you've submitted the response to the letter of questions, or is this something that's sort of upcoming later this year, early, early next year? Yeah, no, I think you're right in terms of obviously working with, you know, CROs and stuff not only with COVID but also the fact that many of the contract organizations are also working on vaccines.
Thats Fair and then just to sort of a zero in a little bit and timeline can you confirm if you've submitted the response to the letter or questions or is this something thats. Our upcoming later this year or early early next year.
Yeah, No I think you're right in terms of because obviously you know obviously working with.
See our own stuff with not only with Covance, but also the fact that many of these contract organizations are also working on vaccines and the significant or there are delays within all of this but we've been pushing forward on this and you know.
Matthew Klein: And so there's a significant, or, you know, there are delays within all of this. So we've been pushing forward on this. And, you know, there was, you know, obviously some specific analysis that we need to get done. In order to do that, I'll let Matt go through sort of the timeline and thoughts of the general questions that I'll be asking.
Yes, you know obviously some specific analysis that we need to get done.
In order to do that I'll, let sort of a macro through sort of the time and thoughts on the general questions that we're operating now.
Yes.
Matthew Klein: Yeah, thanks for the question. As you mentioned, these were fairly standard questions that came up during regulatory review, asking for some additional details around some of our assays and additional analyses with them. We had some detailed questions on some of the other aspects of the data, and really, the key time-limiting factor was the fact that the CMOs that we're using to do our bioanalytical assays are also engaged in COVID activities, including labs that do diagnosis as well as help develop therapeutics. And so we've had to take a little bit of a backseat to those COVID-related activities. I see.
Thanks for the question. So as Steve mentioned these were fairly standard and questions that come up very regulatory view asking for some additional details around some of our assays and additional analyses with them and skip some detailed questions on on some of the other aspects of the data and really the key.
The time limiting factor was the fact that the CMO those that were using to do I buy analysts. Our assays are also engaged in covert activities, including labs, and David diagnosis as well as talked about therapeutics and so we've had to take a little bit of a backseat actually those kobe related activities and that's what's delayed our responses to questions.
We're in the process of getting those resolved to help to have seen as possible and that's why we're saying that we expect the final cgmp opinion in each one.
Unknown Attendee: Very helpful. Thank you very much and congratulations again on all the progress. Thanks a lot. Our next question comes from Robyn Karnauskas. From Truist Securities, your line is open.
I see very helpful. Thank you very much and congrats again on the progress.
Okay. Thanks, a lot.
Our next question comes from Robyn Karnauskas with truly Securities. Your line is open.
Hi, Thanks for taking my question I'm, just first them how many 10. So I think you can occur if announced that they will be doing a controlled blinded study for their initial on trial in Huntingtons and that's it came from the FDA suggestion, maybe comment a little bit about your thoughts fine.
Robyn Kay Shelton Karnauskas: Hi. Thanks for taking my question. Just first on Huntington, so I think Unicare has announced that they will be doing a controlled blinded study for their initial trial in Huntington, and that came from the FDA suggestion. Maybe comment a little bit about your thoughts on why not do a controlled study, a blinded study, so that maybe you have earlier approval. And then the second question is on AADC, or actually on PQ and AADC-PQ. Give us more timelines regarding that program. Like, what are your thoughts on the timelines for the trial?
Why why not do a controlled study like a blinded study so that maybe your earlier approval and then second question is on HBC Brexit PQ in HCP can you give us more timelines regarding up that program like what do you what are your thoughts on the timeline for the trial and then I'll have a follow up thanks.
Unknown Executive: And then I'll have a follow-up. Okay, so you said we're going in and out a little bit on the Huntington's, but basically where we are within the Huntington's trial and why not do a placebo control, is that what the question was? Why not blinded? Why not blinded?
Okay. So.
You sort of were going in and out a little bit on the funding.
Huntington's, but basically.
Where we are within the hundreds and trial and why do not do a placebo controlled what was the question was why not blinded why not blinded. The f. gave sort of suggested to them a blinded, they're saying that after you suggested a blinded trial. So that that you thought it might be the potentially yeah.
Unknown Executive: The FDA sort of suggested to them a blinded trial, they're saying the FDA suggested a blinded trial, so that the results might be potentially... Within our trial, it's a placebo-controlled trial as well, and it's a Phase I trial, though. Primarily for safety and the fact that I think we're, in a way, in an unusual position, that even though we're dosing in healthy subjects, so they're not Huntington's patients.
Well, what's in our trial there also.
It's also has its a placebo controlled trial as well.
And then it's a phase one trial, though sleep and <unk>.
Predominantly for safety and the fact that I think we're in being in a way in an unusual position that even though that were dosing in healthy subjects.
They're not Huntington station, we could rapidly do you know pharmacokinetic study. So if you look at the exposures, but because they are Huntington. We can at the same time, we can also utilize the demand or the reduction of hardening phenolic protein. So even in healthy volunteers, it's very analogous to what we did.
Unknown Executive: We could rapidly do, you know, pharmacokinetic studies so we can look at the exposures, but because they have Huntington's, we can, at the same time, we can also utilize this to monitor the reduction of Huntington's RNA protein. So even in healthy volunteers, and this is very analogous to what we did in SMA. And when there are placebo patients in it, it's predominantly to make sure in terms of looking at it safely. So it's blinded through the period of doing it.
In asset May and were there will be both patients and then predominately we'll make sure in terms of looking revenue safely. So its blinded through the theory of doing it and then if you look at the analysis at the end of that so as you know so right now were you know basically good healthy volunteer studies month I mean.
Unknown Executive: And then you look at the analysis at the end of that. So, as you know, so right now, we're basically doing healthy volunteer studies a lot. And the advantage there is we'll be able to define what exposure causes a reduction in Huntington levels. And then from there, we go to Huntington's patients, where we engage with the FDA to design the appropriate study that we can then accelerate. And the advantage again is that even very early on in phase one studies, we're able to look at precisely define the dose that gives us the greatest reduction that we want to treat patients with. And we think that alone is going to help accelerate and bring the drug to patients.
Damage there is we'll be able to find what exposure causes a reduction in the Huntington level.
Levels and then from there we'll go into Huntingtons patients, where well engaged with the FDA.
To design the appropriate studies that we've done to accelerate but you know the advantage again is that we even very early on in phase. One studies, we are able to look at precisely define the dose that give us the reduction for the greatest crop reduction that we want.
Two patients with them, we think that alone is going to help accelerate.
In Britain with drug too.
Patients.
Does that help you. So yes. So do you give a sense of the FDA you know what do you weren't more willing to give a smaller in Huntington study like because they're doing a blinded trial, which is very early stage. So it feels like the f. days more willing to provide more limited patience and a good quality early study I was just wondering if you are getting that sense as well.
Unknown Executive: Does that help you? So, yeah, so do you get a sense that the FDA, you know, would be more willing to do a smaller in-Huntington study, like, because they're doing a blinded trial, which is very early stage, so it feels like the FDA is more willing to approve it for more limited patients in a good quality early study. I was just wondering if you were getting that sense as well, so, you know, from a competitive standpoint. The reason we go into healthy subjects in the beginning is that you can do these studies more rapidly, right? That's the beauty of going into it, right?
So that you know from outside of.
Good point.
The reason we go into healthy volunteers healthy subjects in the beginning is that you can do these studies more rapidly right. That's the beauty of going into revenue because the first thing you really want to do in these studies to find the Doe.
And so this is you know you know gene therapy was so probably not doing one healthy volunteer it's a different path. We have a small molecule and then using phase one studies that you sort of line them up they are healthy subject quick coming they get the drug user they're hooked up on stuff. So you get all the blood.
Robyn Kay Shelton Karnauskas: Because the first thing you really want to do in these studies is to find the dose. And so this is, you know, gene therapy, which they're probably not doing on healthy volunteers. It's a different path.
Multiple times you can look at on a protein levels and so you do this very rapidly then.
Then from there you can define what dose uses exposure that you want to get that reduces the huntington level and that then lets you go into patients right there right, but it is the more appropriate dose that you think could be.
Unknown Executive: We have a small molecule. And then, using phase one studies, you sort of line them up, they're healthy subjects that come in, they get the drug, you know, they're hooked up to this. So you get all the blood at multiple times, and you can look at it on a protein level. And so you do this very quickly. Then from there, you can define what dose gives you the exposure that you want to get that reduces the honeydew level, and that then lets you go into patients right there, but is the more appropriate dose that you think could be, will be. So obviously, there's, you know, no question of the significant unmet medical need for Huntington's disease. And we think that, you know, what's really unique about PBC 518 is that we know it hits directly the reduction of Huntington protein and RNA, passes the blood-brain barrier, the fact that blood gets to every brain cell. So we think there are a lot of major advantages to this, and we think this is the fastest way to get there.
We'll be efficacious.
So obviously there is no question that the significant unmet medical need for Huntingtons disease, and we think that you know what's really unique about.
You know PBC five when they does that is that we know it's directly you know the reduction of Huntington.
Proteins and are a day passes the blood brain barrier its effectiveness in blood gets that every you know great style. So we think there's a lot of major advantages and so we think this is the fastest to get there.
Okay, great. Thank you.
Our next question comes from Alicia Young with Cantor. Your line is now open.
I had internally on clearly good thanks for taking the call and I just want to follow up on ATP sort of curious about your perspective on the line skin activities, especially in Europe.
I mean, a happy green for one and two the early trend really seen supports our confidence in the product and I have a I have a follow up.
Robyn Kay Shelton Karnauskas: Okay, great. Thank you. Our next question comes from Alicia Young with Canter. Your line is now open.
Sure. So I think in terms of.
So what are we doing to get ready for launch I think there's a lot of activities going you know Eric.
Alicia Young: Hey, this is Lian from LinkedIn. Thanks for taking the call. I just want to follow up on ADC, sort of curious about your perspective on the launch, you know, activity, especially in Europe. I mean, you have the screening programs; do the early trends that you've seen support your confidence in the product? And I have a follow-up question. Sure. So, in terms of what we are doing to get ready for launch, I think there's a lot of activities going on. Eric and his team have been working pretty hard on this.
Eric and his team have been working pretty hard numbers, Eric why don't you go through a little bit on.
What we're doing.
Yes of course, Alan Thanks for the question.
Very confident about agency and as I mentioned, the first and most important thing. We've done is to really activate a number of different a key sites in Europe, He law and figured out that a lot of the other local activities, especially.
Using like ABS book Lab.
Because we know in many cases each country has their own preferences in connections about how to screen. So it accelerated a number of those programs and as I mentioned, we're now 17 countries. The 60 day programs.
Unknown Executive: Eric, why don't you go through a little bit on what we're doing? Yes, of course. Thanks for the question. We feel very confident about AADC, and as I mentioned, the first and most important thing we've done is to really activate a number of different key sites in Europe. We've launched and adapted a lot of the local activities, especially using labs, local labs, because we know, in many cases, each country has its own preferences and connections about how to screen.
We're also using an algorithm the algorithm based on a retrospective approach in Europe, and we're using that to partner with various health care providers and this really helps them develop algorithms to execute against satisfy patient base is already well, we can be able to find patients.
And and begin the process of trading down. In addition, one of the key component is ensuring site readiness and at the sites are already are erring not only to just received the violence and treat the patient, but also all the work upfront and after the treatment.
Eric Pauwels: So we've accelerated a number of those programs, and as I mentioned, we're now in 17 countries with 60 different programs. We're also using an algorithm-based kind of retrospective approach in Europe, and we use that to partner with various health care providers. And this really helps them develop algorithms to execute against identified patient bases already, where we can be able to find patients and begin the process of treating them. In addition, one of the key components is ensuring site readiness and that the sites are preparing not only to just receive the vial and treat the patient but also all the work up front and after the treatment to ensure that there's continuity of care. We're doing a lot of work with regard to access to reimbursement.
To ensure that there is continuity of care.
We're doing a lot of work with regard to access reimbursement we're looking at.
The preparing all the dose or to have health technology assessment.
One thing I would remind you is that.
What's unique about.
Our agency gene therapy treatment is that it will be the first approved product in Europe, and no ER will be rolled out as the standard of care and so its not replacing other therapies like like other gene therapies that have been approved for different indication. So.
DC will have its first treatment only treatment in terms of launch sequence it I'm sorry.
Following CHF Ti Paul.
Positive opinion, we certainly will begin the process.
The launching in sequencing many of the countries, which which would include classical like Germany, first and as well as garnering many of the early access programs in Europe, where those are available in southern and northern Europe.
Eric Pauwels: We're looking at preparing all the dosing for the health technology. One thing I would remind you is that what's unique about our AADC gene therapy treatment is that it will be the first approved product in Europe and will be rolled out as the standard of care. And so it's not replacing other therapies like other gene therapies that have been approved for different indications. AADC will have its first treatment and only treatment. In terms of launch sequence, following THFP's positive opinion, we certainly will begin the process of launching and sequencing many of the countries, which would include classics like Germany first, and as well as garnering many of the early access programs in Europe where those are available in southern and northern Europe. Okay, I got it.
Got it that's helpful.
And then on U.S., just trusting study I don't think we've seen the regulatory environment.
It's getting a little bit more conservative. So my question is are you, saying that distribution more PE and still be an approvable endpoint or do you think that they might want to see function data cloud just maybe give us a sense stuff. You are recent discussion with the agency that would be helpful. Thank you.
Yeah, So yeah, I remember when when we.
Talked about business first we when you talked about the discussion with the FDA, which was that they want to really do the one thing that we didn't have was in their minds dystrophin levels in a in the way that they want them to do and to do that experiment, but they do.
Alicia Young: That's helpful. And then on the U.S. distribution study, we're starting to see the regulatory environment getting a little bit more conservative. So my question is, do you think that distribution will still be an approvable endpoint, or do you think the FDA might want to see function data as well? Just maybe give us a sense of your recent discussion with the agency. That would be helpful. Thank you.
Have they didn't look at our data.
I think the say the both the extensive clinical safety data, we save the safety data that we've had this level we have to complete over the trials that we've done and that's why at the end of the day, what they told US is that the dystrophin levels.
Unknown Executive: So we remember when we talked about the discussion with the FDA, which was that they wanted, really, the one thing that we didn't have was, in their minds, a dystrophin level in the way that they wanted them to do and to do that experiment, but they did have, they did look at our data from the trials that we've done. That's why, at the end of the day, what they told us is that the dystrophin level, all that it has to be is over, is that it has to be above the background. That's, and it has to be statistically significant.
That all that it has to be as over is the it has to be above the the back row. That's.
And it has to be statistically significant and that along with.
The clinical data that we have.
Is would be sufficient for.
Oh accelerated approval with study 41 after completion would be bad for full approval and I think that's.
You know is appropriate if you think about other companies that they've gotten approved on dystrophin alone without any sort of data of clinical benefit. So I think we have to combination hopefully with the the results to come out so that we will see this for for the data center along with the clinical data that we have.
Unknown Executive: And that, along with the critical data that we have, would be sufficient for accelerated approval, with 741 after completion would then be for full approval. And we, you know, I think that. [inaudible] And then we have the trial that's ongoing, which would be for full approval. Thank you very much.
Yes, well actually be a nice strong path.
Both clinical benefit as well as Brazil or something and.
And then we have the trial design going that would be for full approval.
Thank you very much.
Thank you. Our next question comes from Joel Beatty with Citi.
Joel Beattie: Thank you. Our next question comes from Joel Beattie with Citi. Your line is now open. Hi, thanks for taking the questions. The first one is on TransLarna in Brazil.
Hi, Thanks for taking the questions. The first one is on Translarna in Brazil I'm for the recent order there could you characterize how the.
Eric Pauwels: For the recent order there, could you describe how the pricing and volume compares to the previous bulk orders from Brazil? Yes, sure. Eric, do you want to talk a little bit about... Yeah, Joe, Brazil's pretty lumpy in terms of their orders. And I can say that, first of all, I'm really proud of the PTC Brazil team that has been managing what I think is a very, very challenging situation right now in Brazil. The country has been hit exceptionally hard by the pandemic. COVID-19 has disrupted not only the administrative aspects of it, but just the way healthcare has been sort of spending has been diverted. We know many companies haven't received any orders over the years.
Pricing and volume compares to the previous bulk orders from Brazil.
Yes sure.
Thank you want to talk a little bit about that.
Yeah.
In Brazil, Brazil pretty lumpy in terms of their orders that I can say that work.
Well first of all I'm really proud of the PTC, Brazil team that has been managing what I think is a very very challenging situation right now in Brazil. The.
The country's been hit exceptionally hard by the 10 that gain has disrupted.
Not only the administrative aspects of it but just the where the way healthcare has been sort of AD spending has been diverted you know many companies haven't received any orders here. So the team there really has done a terrific job to work with advocacy groups and health and key opinion leaders and others to really sort.
Eric Pauwels: So, the team there really has done a terrific job working with advocacy groups and health and key opinion leaders and others to really sort of bring about awareness that patients shouldn't be off treatment. Now, we don't necessarily give out specifics, but what we're happy about here is that the order was substantial enough to cover not only the existing number of patients but also a substantial number of new patients that have been diagnosed and have gone through the judicialization process. So, I'm very pleased that we're able to get drugs to patients this year and that continuity will be in the first half of next year as well. Thanks for that!
Yeah bring about awareness that that patient should begin to be off treatment. I mean, the good news is that we continue to find cases, and we've added substantially more patients to a to the order.
And that's important but due to some of the constraints in budget and everything else Minister of health and asked us to split the orders between Q4, which we already received.
And they'll be shipping the second order in Q1, now we don't necessarily give out specifics, but what we're happy about here is that the order with substantial enough to cover not only the existing number of patients, but also a substantial number of new patients that have been.
Joel Beattie: And one other question on AADC. Could you help characterize what needs to be completed between now and the NDA filing? You know, and part of the reason I ask is that recently, you know, there was some hope that the filing could be by the end of this year. And now it seems to be in the first half of next year, which seems to be up to a six month delay. So, you know, what may be the reason for the extending of the timeline?
<unk> dose and had gone through the judicial innovation process. So I'm very pleased that were able to get patient drug to patients. This year antibiotic continuity will be in the first half of next year as well.
Got it thanks for that and then maybe one other question on Hey, do you see could you help characterize what needs to be completed between now and the Anda filing in part of the reason I ask because it seems like recently there was some hope that the filing could be by the end of this year and now right.
Unknown Executive: Yeah, so I'll start and then I'll, I'm going to have to go into a little bit more detail, but part of this is really a lot associated with the pandemic. And obviously, we've talked previously about the surgical features as a gauge factor to get a few additional patients in, and the pandemic has been an issue for us, but we're expected to complete it now in the fourth quarter. Matt, do you want to talk a little bit about what's needed after that?
Now seems to be in the first half of next year, which seems to be up to a six month delay. So you know what maybe a accounts for the extending the timeline.
Yeah, So I'll start and then I'll ask.
To go into a little bit more detail, but part of it is really a lot of associated with.
The pandemic and obviously, we've talked previously about the surgical features as a gating factor to get a few additional patients send them up and dynamic has been an issue for us. So were expected to completed now in the fourth quarter.
Matt you want to talk a little bit of what's needed after that.
Matthew Klein: Yes, sure. As you mentioned, and we've talked about before, one of the key gating items for the BLA was fulfilling an FDA request to treat patients with the cannula that we're going to use commercially. And a cannula is the device that delivers the gene therapy into the precise area of the brain. And we had those surgeries scheduled in the third quarter. They've gotten delayed due to COVID and are now scheduled for the fourth quarter.
Yes, sure. So as you mentioned and we've talked about before one of the key gating items.
For the L.A. was filling an empty request to treat.
Patients with Dick can you know that we're going to use commercially in the canyon was going to face that lingers the gene therapy into the precise area of the brain and we had those surgeries scheduled in the third quarter, they've gotten delayed due to covenant house schedules on the fourth quarter. So the expected do those procedures now again the important thing here is to study and.
Matthew Klein: So we expect to do those procedures. Now, again, the important thing here is the study of the cannula, not the safety of gene therapy or the efficacy of gene therapy but basically demonstrating that we can get the gene therapy to the right location without any procedural complications. So the plan will be to gather data from those procedures and then make sure we're aligned with the FDA and move forward with the submission. As you mentioned, obviously, we're well aware of the evolving landscape in gene therapies and some of the feedback that the agency has given to other companies. We're obviously watching that very closely.
The kanuma not the safety of the gene therapy, and the efficacy of gene therapy that basically demonstrating that we can get the gene therapy to the right locations without any procedural complications. So the plan will be to gather the data from those procedures and then make sure were aligned with the FDA and move forward with the submission.
As you mentioned, obviously, we're well aware of the evolving landscape in gene therapies and as some of the feedback that the agency is some of the other companies. We're obviously watching that very closely. That's also why we want to make sure that we have the data that we are aligned and move forward and we expect that we'll be able to do that moves or make a deal a submission in a.
Joel Beattie: That's also why we want to make sure after we have these data that we are aligned and move forward, and we expect that we'll be able to do that, move forward with the BLA submission in H1 in 2021. I also want to emphasize that we remain incredibly enthusiastic about the program because one of the things we've been able to do during this delay is continue to harvest long-term data from the patients that have already been treated. And this package is a very strong package with long-term follow-up, 5, 6, 7, 8 years of therapy. We're able to demonstrate the durability of dopamine production as well as the durability of clinical response. And we know that the durability of the treatment effect is really a crucial aspect of a gene therapy pathway. So we look forward to being able to have the procedures done, addressing any other issues with the agency, and moving forward with presenting this package to you. Yeah, that's helpful. Thank you. Our next question comes from Joseph Dohm with Cowen. Your line is open.
Each one in 2021 I also want to emphasize that we remain incredibly enthusiastic that the program is one of the things we've been able to do during this delay is continue to harvest long term data from the patients that have been treated already and this package is a very strong package with long term follow up by six cents.
Seven eight years on therapy were able to demonstrate durability of doping me production as well as Derbio durability of clinical response, and we know that durability of treatment effect is really a crucial aspect to a gene therapy package.
So we look forward to being able to have the procedures done aligning on any other issues with the agency and moving forward with that with that presenting this package to the agency.
That's helpful. Thank you.
Our next question comes from Joseph Stone with Cowen Your line is open.
Hi, there. Thank you for taking my questions.
Joseph Patrick Schwartz: Hi there, thank you for taking my questions. On Vatiquinone and Phragocataxia, can you remind us, is there a reduction in the FAR score that physicians highlight as clinically meaningful around that 72-week timeframe that you're looking at, and are you making any considerations regarding patient enrollment depending on disease severity? And then, on a related note, now that HopeWell is online, can you give us any updates as to when you expect to submit the IND for your Phragocataxia gene therapy? Thank you. Sure, let's start with Matt. You want to... Go ahead.
On mystic one on in ticket Akcea.
Can you remind us is there a reduction in the Fars score the physicians highlight as clinically meaningful around that 72 week timeframe that you're looking and are you, making any considerations regarding patient enrollment depending on disease severity and then on a related note now that Hopewell is online can you give us any update.
So when you expect to submit the R&D fear for detecting therapy. Thank you.
Sure.
Let me start with Matt you want to.
Oh go ahead, yes.
Yes, really sort of the the phase three essay a seven.
Sevenforty seem to move that paid trial is one that we're building on a a body of experience and our own clinical studies as well as those of others. One of the most in a couple of important points one as Steve mentioned that target and then the last 743 to our opinions on 15 like oxygenate and the associated pathway of inflammation and Ionis oxidative stress.
Matthew Klein: Yeah, absolutely. So the Phase 3 FA-743, the MOVE FA trial, is one that we're building on a body of experience in our own clinical studies as well as those of others. One of the most important points, one is to mention the target in MOA of 743 targeting the enzyme 15-lipoxygen. And the associated pathway of inflammation and ironase oxidative stress is clearly one that's shown to be incredibly important to FA pathology.
Is clearly one that is shown to be incredibly important to ethane psychology and on top of that we obviously have the phase two data, which demonstrated over a prolonged period of treatment. After 24 months, we had a significant reduction.
In the fourth quarter, which translates to a significant improvement of disease severity just to give you. An example of that but the overall improvement in those treated was increasing to 1.8 points on as far as relative to the natural history match cohort, which was a worsening of 4.8 points. So we think that is a significant magnitude of effect relative to the understood natural.
Matthew Klein: And on top of that, we obviously have the Phase 2 data, which demonstrated that over a prolonged period of treatment, after 24 months, we had a significant reduction in the FAR score, which translates to a significant improvement in disease severity. Just to give you an example of that, the overall improvement in those treated was an improvement of 1.8 points on the FAR as relative to the natural history match cohort, which was a worsening of 4.8. So we believe that this is a significant magnitude of effect relative to the understood natural history of the disease. And so we do expect to have a clinically, clinically meaningful effect on the MFARs. In addition, I think, as we're all well aware, is the FDA's desire to have an endpoint strategy that would not only include the MFARs but also key secondary endpoints that reflect key aspects of feel and function.
History of disease, and so we do expect to have a clinically clinically meaningful effect on the M. far. In addition, I think as we're all well aware of it is the Fccs design.
Desire to have an important strategy that we not only include the MSR is that also a key secondary endpoints like that reflect key aspects of feeling function and those of course are going to be the activities daily living and walk test, which is an endpoint strategy that we've aligned with both the FDA and EMA.
Because we realize thats a crucial aspect to disease. The selection of the 18 month duration of apparel offer simple controlled phase again is based on our own experience as well as that of countless others, where there is a placebo effect that put in in future attacks. It does present, even at six months and sometimes longer than we believed by being able to.
Treat for 18 months, we'll be able to again see what we saw in a phase two study in which was a long term effect on disease progression and also I'm, a dampening and hopefully elimination of that placebo effect, which of course is still incredibly important to be able to then demonstrated statistically significant effect on the MSR scale regarding your question about disease severity.
Matthew Klein: And those, of course, are going to be the activities, daily living, and walk tests, which is an endpoint strategy that we've aligned with both the FDA and EMA on because we realize that it's a crucial aspect of the disease. The selection of the 18 month duration of the parallel placebo control phase, again, is based on our own experience, as well as that of countless others, where there is a placebo effect that occurs in free trichotaxia that is present even at six months and sometimes longer.
Obviously, we understand that disease severity as important aspect to Threeg tax hit also can impact the potential response to therapy and ran it progressing to dose and placebo groups and while we do not only will have a range of agriphar scores to book in that disease severity also plan to stratify Randomization Army Air force to ensure that we are balanced.
Between both the treatment and placebo group on this critical SAP.
Great. Thank you and then the last one.
The second part was just on the di Andy for that particular oxygen therapy.
Joseph Patrick Schwartz: And we believe by being able to treat for 18 months, we'll be able to, again, see what we saw in a phase two study, which was a long-term effect on disease progression and also a dampening, and hopefully elimination, of that placebo effect, which, of course, is so incredibly important to be able to then demonstrate a statistically significant effect on the MFAR scale. Regarding your question about disease severity, obviously, we understand that disease severity is an important aspect of trichotaxia and also can impact the potential response to treatment and rate of progression compared with those in the placebo group. And while we not only will have a range of MFAR scores to bookend that disease severity, we'll also plan to stratify our randomization on the MFARs to ensure that we have balance between both the treatment and placebo groups on this critical factor. Great, thank you.
Bringing hope all online kind of give little bit more clarity on when when that can be submitted.
Yeah, I think we're.
We're pretty enthusiastic still about the frankly, the gene therapy on the lead some centers that were working on.
And to support it and we'll like to.
As we move forward on that we'll be able to give you a more precise update on the timing.
Great. Thank you very much.
Our next question comes from rising facade from William Blair. Your line is now open.
Thanks for taking the question just a follow up on some of the comments made on the Dystrophin study still would you mind sharing just what the kind of Delta is first since its real significance above background.
For for for the study and then I've a follow up.
Sure I'll start.
For them to.
Hi, Matt.
That's an important point there is no real and actually you might remember when Dr was talk talk about this but with the two sensors, particularly from some of the approval, but there was no precise number of just the front back from the prison to that being said I was quite.
Is quite analytical and very sensitive so that you know we should be able to monitor.
Monitor and see what football background and in terms of the level that you want to talk a little bit about the CRL and where we are on that.
Unknown Attendee: And then the last, the second part was just on the IND for the Fretricotaxia gene therapy. Does bringing Hopewell online kind of give a little bit more clarity on when that could be submitted? Um, yeah, I think we're still pretty enthusiastic about the G-Therapy and the Agelman Center that we're working on and supporting it. And we'll, you know, I think as we move forward on that, we'll be able to give you a more precise update on the timing. Great. Thank you very much. Our next question comes from Raju Prasad with William Blair. Your line is now open.
Yes, certainly as you said, we recognize that.
Finally, what we know from our experience at the same that we're seeing with instructor studies and then as far as most of whom who have recently had approvals based on the dystrophin endpoint alone.
We know that there's typically very low levels of dystrophin expression at baseline in patients and therefore, it was incredibly important for us to develop an assay that was incredibly sensitive right, we really want to be able to capture those lower levels of dystrophin expression, because we want to show them that way.
Can have that improvement over based on statistical significance that we need.
Unknown Executive: Thanks for taking the question. Just a follow up on some of the comments you made on the dystrophin study. Stu, would you mind sharing just what the kind of delta is for significant above background for the study, and then I have a follow up. Sure, I'll start and then I'll pass it on to Matt.
And so what we've done and obviously setting up. This study is modeled the number of different scenarios, assuming low levels of baseline dystrophin expression and looking at potential increase in district baseline coefficient of variation to ensure that our 20 subjects that we have more than sufficient power to demonstrate a statistically significant improvement over pace.
Fine, which really was the threshold I think you should see a battery established for us, but obviously the established for others as well.
Unknown Attendee: For us, the important point, there is no real, and actually, you might remember when Dr. Woodcock talked about this basically, that she said, in particular in terms of the approval, that there was no precise number and just the background was sufficient to show that the ECL is quite. [inaudible] Yeah, absolutely. As you said, we recognize that, finally, what we know from our own experience that the same that was seen with insurrective studies and NS Pharma, both of whom have recently had approvals based on the dystrophin endpoint alone, we know that there are typically very low levels of dystrophin expression at baseline in patients. And therefore, it was incredibly important for us to develop an assay that was incredibly sensitive, right? We really want to be able to capture those lower levels of dystrophin expression because we want to show that we can have that improvement over baseline statistical significance that we need.
Great and on the commercial franchise, you know, obviously, you know covance kind of spiking up again going into the into the fourth quarter or is there anything that maybe you guys could give us some color on expectations.
For trends all of them in flaws or into the fourth quarter, given the potential headwinds or any learnings you have from the second quarter.
And then on rent the clamor brizzi looks a good number that the split between two and three type two and three and type one.
Do you think that that's just a function of of the nature of the disease and the prevalence of the disease or are you seeing something from early adopter physicians on being more willing to prescribe to student three patients. Thanks.
Yeah sure. So you know from the sort of you know in terms of we screen. These trends London flaws are really <unk>.
It was very good performance from the portfolio that.
We've been doing both pharma and plaza.
And so.
Even in spite of code.
In someone's because even with co good.
So I'm actually quite well.
The insurance company almost.
Unknown Attendee: And so what we've done, and obviously setting up this study, is modeled a number of different scenarios, assuming low levels of baseline dystrophin expression and looking at potential increases in dystrophin baseline, coefficient of variation to ensure that with our 20 subjects, we have more than sufficient power to demonstrate that statistically significant improvement over baseline, which really was the threshold that the agency has not only established for us but, obviously, established for others. Great And on the commercial franchise, you know, obviously, COVID is kind of spiking up again going into the fourth quarter. Is there anything that maybe you guys could give us some color on expectations for TransOregon Plaza into the fourth quarter, given, you know, potential headwinds or any learnings you have from the second quarter?
Allowing more through the subject brew, so boot pose for Translarna middle class or was it pretty good.
Production could talk more about that as well, but the tougher to resupply them I think the fact that its orally bioavailable distributed directly to patients is a really big advantage.
And to some people have been able to continue with that Mary you want to put a little more color on this.
Yes sure Steve.
I think first of all as you mentioned the DMD franchises in a really strong position and we're continuing to see growth quarter on quarter and year on year, especially.
Especially strong growth from the clause that with over 60% growth from the previous quarter, and we anticipate that growth to continue into well into the fourth quarter.
Main drivers there have been again hot new prescriptions, we had.
Great response, so far in the quarter with new prescriptions in the time from that prescription to the time of reimbursement has been very positive weve seen payers that have either eliminated or reduced a lot of the step edits that are involved with prednisone, which is important in terms of timing and the team that we have.
Eric Pauwels: And then on RISDiplam or RISD, you know, looks like a good number, the split between two and three, type two and three and type one. Do you think that that's just a function of the nature of the disease and the prevalence of the disease? Or are you seeing something from early adopter physicians being more willing to prescribe to two and three patients? Thanks.
Really proud of the U.S. team, our PTC kerosene I really focused on the base of patients that we have from Plaza. These patients here have maintain very high compliance well over 90%.
Unknown Executive: Yeah, sure. So, you know, from the 20, in terms of these things for Transylvania and Slaza, really, really very good performance from the portfolio that we've been doing for both Transylvania and Slaza. And so, even in spite of COVID, in some ways, even with COVID, it's done actually quite well. We've, the insurance company's almost been allowing more things to get through. So the folks for Translining the Closet, we've seen pretty good production, and Eric can talk more about that as well. But that's also true with the RISA plan.
That's incredible during the pandemic and seeing I'm very very few dropouts on in Florida as for Translarna. We certainly are seeing growth even in areas that are hit by the pandemic in Europe that we accrued mutations in the quarter in places like Spain, and Italy in.
In France, and other places, where we say covert it really hit them very hard so we continue to see growth.
In all regions.
With trends Lorna and importantly that that is.
Now that we have the quarter in Brazil, I think it's.
It's safe to say that we don't see any major headwind in the quarter.
Eric Pauwels: I think the fact that it's orally bioavailable and distributed directly to patients is a really big advantage. And so people have been able to continue with that. Eric, do you want to add a little more color on this?
Great I appreciate the color. Thank you.
Our next question comes from Brian Abrahams with RBC capital markets. Your line is open.
Hi, This is Steve Allen on for Brian Abrams. Thank you for taking my question on Slide 18, you touched on this just a bit but do anticipate a one to one.
Unknown Executive: Yeah, sure, Stu. I think, first of all, as you mentioned, the D&D franchise is in a really strong position, and we're continuing to see growth quarter on quarter and year on year, especially strong growth from Implaza, with over 60% growth from the previous quarter. And we anticipate that growth to continue well into the fourth quarter. The main drivers there have been, again, new prescriptions. We've had a great response so far in the quarter with new prescriptions, and the time from that prescription to the time of reimbursement has been very positive. So we continue to see growth in all regions with TransLorna. And importantly, now that we have the quarter in Brazil, I think it's safe to say that we don't see any major headwinds in the quarter.
Blubbering depletion ratio will be extended to deep brain structures and given the progressive nature of Huntington's. How early do you think you have to start treating patients to see.
Clinical games.
Yeah Yeah.
Thanks for that yes, so that's the beauty again over of an orally bio available small molecule drug that's across Europe, where you have really good expos.
Within our grasp so we've shown in vivo preclinical studies that the look through not the hundreds of protein.
In all regions, though right.
Were observed.
As a consequence of treatment.
You can see 518.
And that the blood blood levels currently did very well with that right. So I think that that to me that's always been a major damage, especially.
The disease like Huntington's, where you can certainly get you certainly got Brent you get cell death. So.
Brian Corey Abrahams: Great, I appreciate it, Colin. Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.
You know, there's a real real advantage of that so that when in fact you know.
Unknown Executive: Hi, this is Steve Malinow on behalf of Brian Abrahams. Thank you for taking my question. On 518, you touched on this just a bit, but do you anticipate the one-to-one blood-brain depletion ratio will be extended to deep brain structures? And given the progressive nature of Huntington's, how early do you think you'll have to start treating patients to see clinical gains?
Human caused when they do it is to reduce systemic sort reaches all to Susan equally review that.
And where it gets obviously type tradable as well so yes, I think we're in a pretty good.
I believe that that's important to them, but you know you know and this one is the decorative degrees we.
We obviously believe there.
The benefit of reducing costs to come into the basin.
Is this an important obviously to your question you're sort of questions an interesting one from the.
Point of view of trying to treat patients because huntingtons patients.
Unknown Executive: Yeah, so that's the beauty, again, of an orally bioavailable small molecule drug that's brought to where you have very good exposure within the brain. So we've shown in preclinical studies that the loading of the Huntington's protein in all regions of the brain was observed as a consequence of treatment with PCC 518 and that blood levels correlated very well with that in the brain. So I think to me that's always been a major advantage, especially in a disease like Huntington's where you can certainly get, you know, you certainly get brain, you get cell death. So, you know, there's a real, real advantage to that.
Obviously, they take time as there is no no way to predict when you're when you'll be able to do that so the notion of being able to do in prodromal patients well nice.
It is hard to do because you don't know how long the study would be so I think you need to start with in terms of clinical trial.
[music].
With man patient.
Oh permanently right. Because then you you know there have you have something we can measure.
Oh look at the speeds of of course of disease.
So were you know obviously, we're starting early booking that manifests too soon but we're looking obviously to treat all patient types, including <unk> book, you know not only the manifestations, but you know there's the juvenile patients was so rapid onset and clearly that's something we should look at it as well because.
That occurs early and it goes more rapidly so that.
Unknown Executive: So that, and in fact, you know, PTC-1518 is systemic, so it reaches all tissues and is equally distributed, and it's obviously titratable as well. So, yeah, so I think we have a pretty good belief that that's important, you know, and it's a degenerative disease. We obviously believe the benefit of reducing toxic honeydew in the patient. Unknown Speaker 08.01.12.22 Unknown Speaker 08.01.22.23 Unknown Speaker 08.01.22.23 Unknown, [inaudible] Ultimately, right?
Well and then ultimately you want to get to Perjure prodromal patients.
And moving so that once you know more of that because.
Obviously open to where you want to get the patient well before they're manifesting that but you know the first step is to show that you can offer in the course of the disease understood do you understand the learnings from that and then I'll move as rapidly as possible as possible in CRE book J.C.
During world.
So we're going to be learning over time as we do this but I think the really you know from my perspective is the.
Really good.
News from US is that we know we're you know and the fact that it's our own I remember blot the see the reductions we know we're on target now it's about really just like we did enough for me to demonstrate clinical effect.
Unknown Executive: Because then you, you know, they have, you have something we can measure. You know, look at the stage of the course of the disease. So, you know, obviously, we're starting early, looking at manifest patients, but we're looking obviously to treat all patient types, including, you know, not only manifest patients, but also, there are the juvenile patients, which show rapid onset, and clearly that's something we should look at as well, because that occurs earlier and goes more rapidly, so that's a potential as well. And moving to that once you know more of that because, you But, you know, the first step is to show that you can open the course of the disease, understand the learnings from that, and then move as rapidly as possible into both JHD and prodermo.
Thank you Jim.
Our next question comes from Gena Wang with Barclays. Your line is now open.
I think if anything our questions. This is David dye on Cortina. So one question on the Hdc program. So since the C.H.M.P. opinion would be on first half of next year, well actually in reimbursement discussion with paralyzed what's consideration for pricing and then I planning.
For installment I, you stop him as well.
Yeah sure so.
Obviously, the agency program and the results that we have are really quite compelling.
And we've done a lot of work in terms of working clearly, it's an easy one to see the effects of this drug.
Eric maybe you want to talk a little bit about all the work that we've done in terms of getting ready.
Unknown Executive: So, you know, and we're going to be learning over time as we do this, but I think the really good news from us is that we know we are, and the fact that it's oral and then when you look at blood to see the reductions, we know we're on target. Now it's really just like we did an SMA to demonstrate clinical effect. Thank you. Our next question comes from Gina Wang with Barclays; she'll unmute. Hi, thank you for taking our questions. This is David Dai on behalf of Gina.
Yeah and that ready assets.
I see I think it's interesting because we've been getting ready now for a long time and we're ready to go because we have been studying patients.
And we have very strong data as a reminder, when we go forward with our H.T. assessment by which we have had multiple early payer discussions in Europe, those who have early access mechanisms and those who are going to pull the drug more commercially after approval, but what we try to emphasize more than anything else.
This is that this is a high unmet need.
Unknown Attendee: So one question on the AADC program. So since the CHMP opinion will be on the first half of next year, what has been reimbursed in discussion with payer life? What's the current consideration for pricing, and then are you planning for installation payments as well?
There is no tricks that currently available for the poor pay her children with APC and that all children with 80 seeming to be a need to have this treatment and importantly that when treatment is given there's there's durability. We have data now that goes out in some cases for five years seven years, we have.
Patients that are treated even longer than that so from a health.
Unknown Executive: Yes, sure. Obviously, the ABC program and the results that we have are really quite compelling, and we've done a lot of work in terms of looking. Clearly, it's an easy one to see the effect of this drug. And, you know, Eric, maybe you want to talk a little bit about all the work that we've done in terms of getting ready. Yeah, and that's fine.
Health care Health Technology assessment perspective, we're bringing a new standard of care and we're bringing the only standard of care. So the pricing will reflect a number of different things get ROE as well as in the United States and we've been very good at maintaining a very narrow pricing corridor.
Across Europe and across international markets, but it will certainly be based on the population that is addressable the unmet need and of course, the willingness to pay and the mechanisms by which each country will have.
Eric Pauwels: It's interesting because we've been getting ready now for a little, a long time, and we're ready to go because we have been studying patients, and we have very strong test data. And as a reminder, when we go forward with our HTA assessment, which we have had multiple early period discussions in Europe, those who have early access negativisms and those who are going to approve the drug more commercially after approval, what we try to emphasize more than anything else is that this is a high-end need. There is currently no treatment currently available for this, for children with AADC, and all children with AADC need to be, and need to have this treatment.
Well as I mentioned earlier, we anticipate to have our first commercial launches in the traditional markets in Europe, such as Germany, where approval or free pricing would have.
First benefit and then we would we would subsequently go to a number of the markets that have already asked us about early access programs. So many of those those countries in southern Europe would be targeted as well I think and following the European approval, we will be targeting other markets outside of Europe the ticket.
In Latin America, and potentially Asia Pacific.
So our pricing strategy, where we will discuss price at this point in time will certainly not be based on a replacement of a product, which other gene therapies are but has an established standard of care a new standard of care that will make a high unmet need big bird and and it's relatively small.
Eric Pauwels: And importantly, that when treatment is given, there is durability. Thank you. I got it.
Population five patients worldwide.
Unknown Attendee: That's really helpful. Actually, another question on the BIO-E 743 program for mitochondrial epilepsy. So you're going to be administering it as a TID dose. So what's the pill burden like? And can you just provide some more color on the PK profile of the drug, including the half-life, the Tmax, and also any foot effects? Sure, Matt, do you want to go?
Got it that's really helpful and so just a follow up actually another question on the ballot E. Authentic what do you see program format. A contrast, let street on so you didn't need a midstream should T.I.D. dosing so.
So what's the appeal bring them like and these can you just provide some more color on the PK profile of the drugs, including the half life of the T. Max and also any food effect.
Sure Matt do you want to go.
Matthew Klein: Yeah, absolutely. So 743 is a TID dose medication. Obviously, we've been treating patients for a number of years and also understand the pharmacologic parameters of the drug quite well. It's given three times a day with food. It can be administered, and it's administered as a solution for young children, which is particularly helpful given that many children with mitochondrial disease, including those with mitochondrial disease or refractory seizures, are feeding tube dependent. So being able to administer the drug through a feeding tube in solution form is quite convenient. And then, of course, it's three times a day, breakfast, lunch, dinner; it's given with the meals.
Absolutely. So 743 is a t. I'd dose medication, obviously news we've been treating patients for a number of years and also understand the pharmacologic private owners of the job quite well.
It's getting three times a day its food or it can be administered it's administered as a solution for young children, which is particularly helpful. Given that many children its mitochondrial disease, including those with a lot of controversy sorry factory seizures of eating too dependent so being able to administer the drug feeding tubes quite willing solution foremost by convenient and then.
Of course, it's three times a day breakfast lunch dinner, it's keeping with meals and that three times a day dosing regimens, obviously generated given the half life of the drug which is between two and four hours a day in patients.
Matthew Klein: And that three times a day dosing regimen is obviously generated given the half-life of the drug, which is between two and four hours in patients. And so, obviously, again, we have a dosing regimen that's been well-informed based on previous pharmacologic evaluations, as well as, obviously, the safety and efficacy record of the drug. Thank you so much. And the next question is a follow-up from Vincent Chin on Bernstein. Your line is now open.
So.
Obviously again, yes dosing regimen is going well informed based on previous pharmacologic evaluations as well. Obviously this is to say to that to see that kind of of the of the drop.
I think it's so much.
And next question is a follow up from the tension with Bernstein. Your line is now open.
Unknown Attendee: Great. Thank you so much for taking the follow-ups. I have a couple of deep in the weeds follow-ups on Huntington's, if you're amenable. The first is simply, I'd love to dive a little deeper into what's the minimal amount of knockdown or range of knockdown you're looking for.
Great. Thank you so much for taking the follow ups on a couple of deepened. The we just follow ups on Huntingtons, if you're if you're a minimal. The first is simply looked to dive a little deeper into whats the minimal amount of knockdown or range of not going you're looking for I know, some 50% plus oil weighted 80% or so in mice, but imagine lesson as maybe it may well be at a good, especially given sort of a uniform.
Unknown Executive: I know you've shown 50% plus all the way to 80% or so in mice, but I imagine less than this may well be adequate, especially given sort of a uniformity of distribution throughout the brain. And I also wonder, is there some point at which you worry about loss of function, or adverse effects from excessive knockdown? And the second question is, I'd be curious to get your thoughts on how you expect a likely dosing range could compare to, I guess, for the sake of an easy comparator, RISD-PLAM. Basically, your preclinical studies, are the pharmacokinetics for the Huntington's program comparable to RISD-PLAM? And how high can you go on dose from a safety perspective based on what you've seen preclinically? Yeah, no, thanks.
Do you have distribution build the brand and I also wonder is there some point at which you worry about loss of function adverse effects from from excess knockdown.
And the second question is on.
We could get your thoughts on how you expect the likely dosing range could compare to I guess for the sake of an easy compared or receive Lam.
Basically a preclinical studies or are the pharmacokinetics for the hunting gisbergen comfortable the redeployments how high can you go on dose from a.
From a safety perspective based on what you've seen preclinically.
Yeah no. Thanks once appreciate that.
So the question on what goes up you are you seeing the pre clinical results in the nice aspect.
Unknown Executive: I appreciate that. Then, you know, so the question on what goes out, yeah, you've seen the free clinical results on the knife aspect. [inaudible] You know, once a day, doses or so, and that's our expectation, but we'll obviously be able to measure the effect in the blood and adjust accordingly. It's hard to actually say until we put it in the humans, but that's our expectation. We think it'll be in some way similar to what you're saying with the RISDA plan, that it's a once-a-day dose. That's somewhat our expectation, but we always wait and see how it does in humans.
Oh over an orally bio available on drug is that it was price tradable.
And you can get in there for you to talk to the level that you want to get too.
Obviously, I think what the community to somewhere.
Up to 50% when the goods are still discussing for between 30% to 50%.
The associated with therapeutic benefits based on some.
Preclinical results. So we're shooting in that runs a CRE benefits as a consequence of that and.
And we think we'll certainly be able to do that Oh, you will probably will.
You know once a day dose bigger so.
Unknown Executive: Thanks for the question. Unknown Speaker Oh, your question on, yeah, you know, I think a lot of, you know, we're thinking about the question you had in terms of, you know, what are in terms of what we think you probably can go substantially down post-development. And that's something we ultimately want to look at if we can, but we think that 30 to 50% of that range would be just fine to be able to do it. But we do sort of, you know, think about how high you can go. I mean, obviously, higher is even better.
That's our expectation but.
But we'll obviously be able to measure the effect in blood and adjust accordingly.
So you know and that will be up you know so you know it's hard to say until we put them in humans, but that's our expectation. We think it will be you know in us in some way similar to what you're saying with.
Is the plan, but it's a once a day dosing.
That's somewhat of our expectation, but you know you always wait and see how it doesn't in humans.
[laughter].
Yes, sorry go ahead.
Oh your question on Yeah, you know I think a lot of you know.
We're thinking about the question you had in terms of whether in terms of the Wi fish you probably can go.
Absolutely down post develop and that's something where we ultimately want to look at it if we can but we think that 30% to 50% of that range would be just fine there, but we'll do it but we do start to think about.
How high can you go through obviously.
Sure, that's even better but we're just trying to figure out some of this out and experimental.
Unknown Executive: But we're just trying to figure some of this out and experiment, I see. And then, dose-wise, RISDPLAM, I guess, was sort of limited at the upper end by some of the preclinical safety effects, and I guess you don't need to go that high, so it all works out very well. Preclinically, is there anything that's been seen with RG518 – sorry, PTC518 that would lead you to think that – that basically would put some sort of an upper limit on how high you could work up to in patients or in healthy volunteers?
I see and then I guess dose wise risky plan I guess, what sort of limited at the upper end by some of the preclinical safety. It's actually I think if you don't need to go that high so double it all works out very well.
Pre clinically is there anything thats been seen with or if I want to Oh, sorry.
Hey that would.
Lead you to think that it's <unk> no basically put some sort of a an upper limit on how high you could you can work up to envision or in healthy volunteers.
Unknown Executive: Yeah, you know, in the, you know, non-clinical studies that have led us, I think we have a nice data package that supports us being able to give the doses that we think will be, you know, very much adequate for being able to reduce that. So we feel pretty good that we're in a pretty good spot for this. You know, obviously, we spent a lot of time on this molecule in terms of identifying selectivity, specificity, but also on the pharmaceutical properties. You know, obviously, for us, some of the key things were not that it doesn't pass the blood-brain barrier, that we could get a substantial appropriate level within, and that there was no efflux within the cell. Because if you think of, you know, if you think of a lot of drugs that people take, the reason they don't work for issues in the brain is because even if they could pass the blood-brain barrier, they get effluxed, and so they don't stay within the brain.
Yeah, No I'd say so far.
And the you know Nonclinical studies that have let us I think we have a nice data package.
That supports a premium so the doses that we think will be a.
You know very much adequate for being able to reduce that so we feel pretty good that was a pretty good spot for this.
You know obviously, we spent a lot of time.
On this molecule interval identify and select served with the specificity, but also on the pharmaceutical properties.
No you know obviously, perhaps some of the key things was not it doesnt pass the blood brain barrier. So we did get a substantial appropriate levels within that there was no d. flux with them other cell right. Because if you think of giving a lot of a lot of drug that people take the reason they don't work for.
For Susan who bring us those even if they could pass the blood brain barrier that give you lots and so they don't maintain within the brain and so we've done a lot of work to make sure that they got this drug is not lost on top of having all the rights.
Unknown Executive: And so we've done a lot of work to make sure that this drug is not effluxed on top of having all their, [inaudible] Awesome. Thanks for taking the follow-ups. I appreciate the discussion. Thank you. I appreciate the questions. Thank you, and I'm showing no further questions at this time. I'll turn the call back over to Stewart Peltz for closing remarks. Okay, well, thank you.
Oh property.
You know that it could pass the one can do and get some golf tissue is not new slots. So we feel pretty good about this and so we're looking forward to the results from a phase one trial.
Awesome. Thanks for taking the follow ups I appreciate the discussion.
Hi, Thank you, but I appreciate the question.
Thank you and I'm showing no further questions at this time I turn the call back over to Stuart Peltz for closing remarks.
Okay, well, thank you thanks and.
Unknown Executive: Thanks, and thank all of you for calling in today. And I think, as you can see, despite the challenges that, you know, have been presented by the COVID pandemic, I'm pretty proud of how the PTC team has actually stood and performed during this time. If you think about it, the approval of this was the culmination of many years of discovery and development by our team. And we were also able to complete the biopsy so that we've enabled the potential submission of the TransLarna NDA, and so we're excited about that as well. We've all just started the registrational studies for Tiquinone and Mitochondrial Epilepsy. We initiated and are performing the Phase 1 trial for PTC 857 for GBA purposes, and you know, as you've seen, PTC 508 for honey. So a lot has actually gone on.
Thank all of you for calling in today and I think as you can see that.
Despite the challenges that you don't have been presented by the covert them demick.
I'm pretty proud of how the PTC team has access to them perform during those time to think about it the approval of the.
Was the culmination of many years of discovery development by our teams.
When we were also able to complete.
The biopsy so that does.
Oh that.
But weve been able for potential submission of the trends long enough and D.A. until we're excited about that as well. We are just starting to Registrational studies for took were known and mother comes on epilepsy, we initiated a performing now the phase one trial for the.
Did you see a five cents per GBA purposes.
And we're ready to you know as you've seen PTC five coordinate for Huntington.
So a lot of actually going on we're excited about.
Unknown Executive: We're excited about the future potential of this, really, of all the drugs that we have in the portfolio that we've built, where we're discovering, developing, and commercializing, really, the next generation of value-creating therapies for patients with high medical needs that we think will be quite valuable to all our states. So with that, I want to thank you again for taking the time, for spending some time with me. Have a good evening. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
The future potential of this really of all the trucks that we have in the portfolio that we've built where we're discovering developing and commercializing really the next generation of value, creating bina therapies for patients.
Oh with high unmet medical needs that we see quite value too valuable to all our stakeholders.
So with that I want to thank you again for taking the time for spending some time with us.
I will just leave.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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