Q2 2021 PTC Therapeutics Inc Earnings Call
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Ladies and gentlemen of today's conference is scheduled to begin shortly please continue to standby and thank you for your patience.
Operator: Ladies and gentlemen, today's conference is scheduled to begin shortly. Please continue to stand by, and thank you for your patience.
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Operator: Ladies and gentlemen, thank you for standing by, and welcome to the PTC second quarter 2021 financial results.
Operator: At this time, all participants are in a listen-only mode.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star, then 1 on your keyboard.
Operator: Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I will now like to hand the conference over to your speaker for today, Kyle Leo Keefe, Senior Vice President of Global Commercial and Corporate Strategy. You may begin.
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Kyle Leo Keefe: I am the Vice President of Global Commercial and Corporate Strategies. You may begin.
Kyle Leo Keefe: Good afternoon, and thank you for joining us today to discuss the PTC Therapeutics second quarter 2021 corporate update and financial results.
Kyle Leo Keefe: Joining me on today's call is our Chief Executive Officer, Stuart Peltz, our Chief Development Officer, Matthew Klein, our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Emily Hill.
Okay.
Ladies and gentlemen, thank you for standing by and welcome to of the P. T. C second quarter 2021 financial result at.
Kyle Leo Keefe: Before we start, let me remind you that today's call
At this time all participants are in a listen only mode. After the speaker's presentation.
Kyle Leo Keefe: Today's call will include forward-looking statements based on current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements.
There would be of question and answer session to ask the question 2 on the session you will need of press Star then 1 on your telephone.
Please be advised that today's conference is being recorded.
Kyle Leo Keefe: Our actual results could materially differ from these forward-looking statements, as such statements are subject to risks that can materially and adversely affect the quality of life for individuals.
You require any further assistance. Please press star then zero.
Now I'd like to hand, the conference over to your speaker for today tally Okeefe Senior Vice President.
Kyle Leo Keefe: Transcription by Transcription Outsourcing, LLC. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the Securities and Exchange Commission.
Global commercial and corporate strategy you may begin.
Yeah.
Good afternoon, and thank you for joining us today to discuss the PTC.
C Therapeutics second quarter, 2021, corporate update and financial results.
Joining me on today's call is our Chief Executive Officer, Stuart Peltz, Our Chief Development Officer, Matthew Klein, Our Chief Business Officer, Eric Pouch, and our Chief Financial Officer Emily Hill.
Kyle Leo Keefe: www.pctherapeutics.com.au 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 is available in today's earnings release. With that, I will pass the call over to our CEO, Stuart Peltz.
The full we start let me remind you the today's call.
It will include forward looking statements based on current expectations.
Stuart Peltz: Stuart Peltz. Hey, thanks, Kylie. And thanks for joining us today. As we close out the first half of 2021, I'm proud to say that a lot of progress has been made in all facets of our business. And I'll go into this in more detail shortly.
Please take a moment to review the slides 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 such statements are subject to risks that can materially.
And adversely affect our business and results of operations.
Stuart Peltz: However, before I do, I'd like to take a moment to reflect on our strategic plan at PTC and measure how we're doing. At PTC, our mission is to provide innovative treatments to patients with debilitating diseases that have few or no treatment options. The foundation of our strategy is to have a sustained pipeline so that we may continue to produce commercial treatments that will drive revenue and create value for all stakeholders over both the short term and the long term. We all know the importance of having a deep pipeline to balance the innate challenges of the drug discovery and development process.
For a detailed description of the applicable risks and uncertainties. We encourage you to review the company's most recent quarterly report on form 10-Q, and annual report on form 10-K filed with the Securities and Exchange Commission as well as the companies are the SEC.
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We will disclose certain non-GAAP information during this call information regarding our use of GAAP to non-GAAP financial measures measures and a reconciliation of GAAP to non-GAAP is available in today's earnings release.
With that let me pass the call that the 2 our CEO Stuart Peltz Stuart.
Stuart Peltz: We're all working towards building a steady state number of therapeutic programs so that the successful programs move forward. This approach will allow us to have a sustained pipeline of potential new therapies that reach commercialization and substantially grow our revenue. Though many of us have been fortunate to have access to COVID vaccines, we recognize that the pandemic is still very much a reality in many parts of the world. This brings additional challenges with potential impact across multiple aspects of our business. However, we'll continue to manage through these challenges as they arise.
Instead of Skylake and thanks for joining us today.
As we close out the first half of 2021.
I am proud to say that a lot of progress has been made in all facets of our business and I'll go into this in more detail. Shortly however, before I do I'd like to take the moment to reflect on our strategic.
Part.
PTC a measure of how we're doing.
The PTC our mission is to provide innovative treatments to patients with the.
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You are no treatment options.
Foundation of our strategy is to have the sustained pipeline. So that we may continue to produce commercial treatments.
Stuart Peltz: I want to emphasize the impressive revenue growth that we have seen this quarter, which is driven by the strength in our DMD franchise and the incredible uptick in ERISD. Based on this impressive growth, we'll be raising our 2021 DMD franchise revenue guidance to $370 to $390 million, and Emily will go into this in more detail later in the call.
That will drive revenue and create value for all stakeholders over both.
The short term and long term.
All know the importance of every of those key pipeline the bad.
The unique challenges of the drug discovery in Brazil, a little bit of process.
We're all working towards building the steady state number of therapy.
Keith Graham.
The successful programs move forward. This approach will allow us to have its the same pipeline of potential new therapies that reached commercialization and substantially grow our revenue base.
Stuart Peltz: Our commercial team has been working hard to make our therapies accessible to DMD patients around the globe. As a result, TransLinux saw an impressive 36% year-over-year growth. I'm very proud that the growth continues almost seven years post-launch both in existing geographies and with continued geographic expansion. Implaza is also continuing to deliver strong revenue, with an increase of 36% over the same period last year.
The many of US have been fortunate to have access to Covid vaccine, we recognize that the Pentagon.
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I want to.
Emphasize the impressive.
Revenue growth that we have seen this quarter, which is driven by the strength in our DMD franchise and the incredible uptake of it risky.
Based on this impressive growth, we will be raising our 2021 DMD franchise revenue guidance the.
Stuart Peltz: Eric will discuss the success of the commercial franchise in more detail shortly. Now, let me turn to the splicing platform, starting with Avriz. Aversity continues to see a strong uptake in the U.S., with 1,800 FMA patients now on treatment, representing almost 20% market share in less than a year post-launch. ERISI is also now approved in 53 markets outside of the U.S., and we are starting to see early adoption in these markets and expect this growth to continue as we conclude additional pricing and reimbursement discussions.
$373.90 million.
We'll go into the in more detail later in the call.
So let me start with the DMD franchise.
Our commercial team has been working hard to make our therapies accessible the DMD patients around the globe.
As a result.
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And the M of percent year over year growth.
I'm very proud that the growth continues.
The 7 years post launch both in existing geographies and with continued geographic expansion.
Stuart Peltz: As anticipated, RISD was approved in Japan this quarter, and we will receive a $10 million milestone payment from Roche upon the first commercial sale. I also wanted to touch on the recent positive results from the SMA studies, which I find to be quite remarkable. The Rainbow Fish Study using AVRISDI in pre-symptomatic infants diagnosed with SMA demonstrated that AVRISDI-treated infants achieved the same developmental milestones as healthy children.
I'm proud of is also continuing to deliver strong revenue with the need.
36, 36% over the same period of last year Eric.
Eric will discuss the success of the commercial franchise in more detail shortly.
Now, let me turn to the splicing platform.
With the receipt of.
Where's the continues to see of strong uptake in the U S with 18.
Hundred SMA patients now on treatment, representing almost 20% market share.
Stuart Peltz: Interim data from the Jewelfish study, which is assessing aversity in SMA patients previously treated with other therapies, including Zogentima and Spinraza, demonstrated overall stabilization and motor function after switching to aversive therapy. This shows the benefit of a RISD in the broad and heterogeneous real-world SMA population. Turning to PTC 518 and our Huntington's Disease Program, in the second quarter of this year, we were excited to release the preliminary results from our Phase 1 Healthy Volunteers Study.
Less than a year of post launch.
The rupee is also now approved in 53 markets outside of the U S and we are starting to see an early adoption in these markets.
<unk> of can expect this growth to continue as we conclude on the additional pricing and reimbursement discussion.
As anticipated of risky was approved in Japan, This quarter, and we will receive a $10 million milestone payment from Roche upon the first commercial sales.
I also wanted to touch on the recent positive results from the SMA study, which I find to be quite remarkable.
Stuart Peltz: As a reminder, the results from this study demonstrated a dose-dependent lowering of Huntington mRNA even after only a single dose of PTC518. The results also demonstrated a target mRNA lowering of 40 to 50 percent, even in the lowest multiple affinity dose cohort. We are in the process of completing the phase one trial, which includes additional protein sampling, a food effect cohort, and a CSF pharmacology cohort. We plan to release the results of these additional cohorts in the third quarter of this year, as well as share details on our next clinical study, which we are planning to initiate before year end.
The Rainbow fish study using the rest of the pre symptomatic infants diagnosed with SMA demonstrated that of receipt treated infants achieved the same.
And developmental milestone as healthy children.
Interim data from the Jewelfish study, which is assessing the risk of an SMA patients previously treated with other therapies, including foods and some of it's been rozzer demonstrated the overall stabilization of motor function.
Same wishing to of Brinci.
This shows the benefit of of risky in the broad of energy is real world SMA.
Population.
Turning to PTC 518 in the Huntington's disease program in the second quarter of this year, we were excited to release the preliminary results from.
After the phase 1 healthy volunteer study.
Stuart Peltz: I will now turn to our BioE class. This is an exciting and novel science platform to identify new therapies that result as a consequence of excess electrons, usually produced from the mitochondria during electron transport. This triggers oxidative stress and causes havoc within the cell that results in and exacerbates multiple disease states.
As a reminder, the results from the study demonstrated a dose dependent lowering of Huntington mrna, even after only a single dose of PTC 518.
The results also demonstrated on the target mrna lowering of 40 to 50.
Even in the lowest multiple ascending dose cohort.
We are in the process of completing the phase 1 trial.
This includes additional protein sampling of food effect cohort in the CSF pharmacology cohort we plan to release the results of these additional cohorts in the third.
Stuart Peltz: Drugs that can modulate this process would be valuable therapies to treat a wide variety of diseases. We have two important ongoing trials with our first compound from our BioE platform, which is a 15-leboxogenase inhibitor, which is the key regulator of this pathway. The first is in mitochondrial epilepsy, and the second is in pre-trick attack.
Third quarter of this year as well as share details on our next clinical study, which we are planning to initiate before year end.
I'll now turn to our bio E platform.
This is an exciting of novel science platform to identify new therapies. The result, as a consequence of excess electrons.
Stuart Peltz: These two trials are registration directed and therefore have potential near-term value. We also have a second-generation cysteine lipoxygenase inhibitor, PTC 857, with pharmacokinetic properties well-suited to a range of adult neurodegenerative diseases. We are pleased to have completed the Phase 1 Healthy Volunteers Study for PTC 857, and Matt will share the results later in the call. Turning now to our PKU program, which is another important near-term value driver. We're excited as we plan to initiate the Phase III Registration-Directed Study Affinity in September of this year. PKU is a large orphan indication in an estimated 58,000 patients globally. The vast majority of patients are not well controlled with existing therapy.
Professionally produced from the mitochondria during the electron transport the.
This triggers oxidative stress and causing havoc within the south the result in an exacerbation multiple disease states drugs that can modulate this process would be valuable therapies to treat a wide.
Good variety of diseases.
We have 2 important ongoing trials with the particular note of.
Our first compound from our bio E platform that is of 15 lipoxygenase inhibitor, which is the key regulator of this pathway. The first of is the is in mitochondrial epilepsy and the second is in.
Eureka taxi of these 2 trials are registration directed and therefore, a potential near term value drivers.
We also have the second generation 15, lipoxygenase inhibitor, PTC 857, with pharmacokinetic properties well suited.
Stuart Peltz: Highlighting the Substantial Unmet Medical Needs, Study startup activities are well underway, and we are utilizing our global infrastructure to focus on sites both in the U.S. and globally. PKU is a unique development and commercial opportunity in the rare disease world. As it has a well-defined patient population, well-known centers of excellence, and an expedited path to commercialization, we look forward to the potential of bringing PTC 923 as a clinically differentiated therapy to the PKU community.
And free range of adult in their agenda of the degenerative diseases.
We are pleased to have completed the phase 1 healthy volunteer study or PTC 857, and Matt will share. The results later in the call.
Turning now to our PKU program, which is another important near.
Term value driver.
We're excited as we plan to initiate the phase III registration directed study affinity.
September of this year.
PKU is a large orphan indication within the estimate of 58000 patients globally.
Stuart Peltz: Moving to our gene therapy platform and our AADC program, as a reminder, the CHMP imposed a clock stop to allow for the pre-approval inspection. This process is still ongoing, and we expect to see HFP opinions in the fourth quarter.
The vast majority of patients are not welcome.
Control with existing therapy, highlighting the substantial unmet medical need.
Does the startup activities are well underway and we are utilizing our global infrastructure to focus on sites both in the U S and globally.
Stuart Peltz: Turning to the U.S., as we have previously shared, we were conducting additional surgeries in advance of the DLA submission. We're happy to announce that the third surgery has recently been completed and will now align with the FDA prior to the BLA submission, which we plan to submit by the end of this year. I want to take this moment to discuss our gene therapy manufacturing facility in Hopewell, New Jersey. We have 220,000 square feet.
PKU is the unique development and commercial opportunity in the weird.
Because these world.
As of yet well defined patient population well known centers of excellence and an expedited path to commercialization.
We look forward to the potential of bringing 19 PTC 93 as of.
Clinically differentiated therapy to the PK you community.
Moving to our gene therapy platform and our E. D. C program as a reminder, the see HMP impose a clock stop to allow for the pre approval inspection. This process is still ongoing and we expect to see each of the opinion in the fourth quarter.
Stuart Peltz: Square Foot, Fully Functional, Well Equipped, and Validated Facility for the Development and Manufacture of the Gene Therapy Products in our PIE Program, thereby minimizing our reliance on external CROs. As we have excess capacity and retain the relevant manufacturing expertise, we have a unique opportunity to potentially create a revenue stream by entering into a development manufacturing service agreement with other companies, utilizing this facility and our expertise to produce high-quality plasma DNA and AAV vaccines.
Turning to the U.
The us and we have previously shared we were conducting the additional surgeries in advance of the BLA submission.
We're happy to announce that the third surgery has recently been completed and will now on line with the FDA prior to the BLA submission, which we plan on system. It by the end of this year.
I wanted to take this moment to discuss our gene therapy.
Stuart Peltz: Lastly, I wanted to highlight the potential upcoming milestones from our oncology platform. UNESPOLIN, previously PTC-596, is in clinical trial for two rare solid tumors, DIPG and LMS. CIPG is a rare pediatric brain tumor, and LMS is a rare adult solid tumor in muscle.
Factoring facility in Hopewell, New Jersey.
We have a 220000 square foot fully functional well equipped and validated facility for the development of the manufacturer of the gene therapy products in our pipeline, thereby.
Sure Mike.
Reliance on external C. R O S.
Stuart Peltz: Both have high medical needs, with few beneficial to no treatment options. Results are anticipated in the second half of 2021 for the two clinical trials, and with positive results, we have the potential to initiate registration-directed trials. We look forward to sharing the results shortly. As you can see, we are continuing to make progress across our commercial and clinical applications. I'm proud of our program.
As we have excess capacity capacity and retained the relevant manufacturing expertise, we have a unique opportunity to potentially create a revenue stream by entering into development of the manufacturing service agreement with other companies utilize.
This facility and our expert the expertise to produce high quality plasma DNA and the AAV vector.
Lastly.
I wanted to highlight the potential upcoming milestones from our oncology platform.
Stuart Peltz: We are driven by our people and their strong commitment to our mission to deliver therapy to patients in need. With that, I turn the call over to Matt for an update on developments. Thanks, Kyu.
That's the line previously PTC 5.9.
The minute is in clinical trial for tunes niche solid tumors.
D G and L M S.
D G.
Matt: I want to start by emphasizing the continued progress our development teams have made across all our programs. First, I'll start with our spiking platform and our PTC 518 Huntington Disease Program. As Stu mentioned, we shared the initial results from our PTC 518 Phase 1 Healthy Volunteer Study in the second quarter of the year. As we reported, PTC518 treatment resulted in the desired dose-dependent lowering of HTT mRNA levels in both the SAD and MAD coping.
Rare pediatric brain tumor and the LMS.
Rare adult solid tumor and muscle.
Both have a high unmet medical need with few.
Instead of an official to no treatment option.
Results are anticipated in the second half of 2021 for the 2 clinical trials and with positive results. We have the potential to initiate registration directed trials, we look forward to sharing the results shortly.
As you can see.
We are continuing to make progress across our commercial and clinical efforts.
I'm proud of our progress.
Driven by our people and the strong commitment to our mission to deliver therapy.
Matt: We are in the process of completing additional cohorts to provide data on HTT protein levels and CSF biodistribution. Results from these cohorts will be released in the third quarter of. Given that we have achieved our key objectives for the PTC 518 Phase 1 study, planning for the Phase 2 trial is underway, and we expect to initiate the trial by the end of this year. The Phase 2 study will be conducted in HD patients and will focus on demonstrating dose-dependent reductions in HDP mRNA and protein levels. We will provide more details on the study design once it is finalized.
Patients in the with that I'll turn the call over to Matt for an update on development Matt.
Thanks, Stuart I want to start by emphasizing the continued progress and development teams have made across all our programs.
I'll start with our splicing platform and our PTC 5 on 8 Huntington disease program.
As Steve mentioned, we share the initial results from a PTC 5 on a phase 1 healthy volunteer study.
In the second quarter of this year.
As we reported PTC 508 treatment resulted in the desired and dose dependent lowering of H T. T mrna levels from both the U S. A D and any of these cohorts.
When youre on the process of completing additional cohorts to provide data on HGT protein levels and CSF.
Matt: Next, I would like to highlight the progress we have made in programs for our BioE. We have two ongoing registration-directed trials with ticrinone, our lead compound in the bioethanol. And we recently completed the Phase 1 Healthy Volunteer Study at PTC 856, which is the second compound in the plan.
Bio distribution.
From these cohorts will be released from the third quarter of this year.
Given that we have achieved our key objectives of the PTC 518 phase 1 study planning from the phase 2 trial is underway and we expect to initiate the trial by the end of this year.
Matt: Both the MITEI trial, our Phase II-III trial, and children with inherited mitochondrial disease and epilepsy, and MOVE-FA are global studies that are actively enrolled. As Stu noted, these programs are near-term value drivers, and we remain on schedule to have data readouts with the MITEI study in Q3 2022 and the MOVE-FA study in 2020. Turning now to PTC 857, a 15-lipoxygenase inhibitor being developed for adult neurodegenerative diseases.
The phase 2 study will be conducted in HD patients.
Chris on demonstrating dose dependent reductions in the <unk> mrna and protein levels, we will provide more details on the study design once it is finalized.
Next I would like to highlight the progress we have made in programs from our bio E platform.
We have 2 ongoing registration directed trials with the particular note our lead.
And well thought out from the <unk> platform and we recently completed the phase 1 healthy volunteer study of PTC 857, the set.
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Both the mining trial, a phase III trial in children with inherited mitochondrial disease and epilepsy and move at Phase I Phase II trial of <unk> ataxia or global studies that are actively.
Matt: I am pleased to share that we have completed the Phase 1 Healthy Volunteer Study and that PTC 857 was found to be well-tolerated with no reported serious adverse events. PTC 857 also demonstrated predictable pharmacology, and we were able to achieve the desired plasma exposure levels consistent with the levels at which we observed efficacy in our preclinical study. We are now positioned to move PTC 857 forward to Phase 2. Through its activity at 15-lipoxygenase, PTC 857 targets the pathway of oxidative stress and inflammation known as pharoptosis. Pathway Key to CNS Disease Pathogenesis in ALS, Parkinson's Disease, and Other Neurodegenerative Disorders
We enrolled.
As you noted these programs our near term value drivers and we remain on schedule to have data readouts with the Mighty study in Q3.2022, and the move of FH study from 2000 Twenty's strength.
Turning now to PTC 857 of 15 lipoxygenase inhibitor being developed for adult degenerative.
The say I'm pleased to share that we have completed the phase 1 healthy volunteer study and the PTC by setting the strategies well tolerated with no reported serious adverse events. PTC 857 also demonstrated the predictable pharmacology and we were able to achieve the desired plasma exposure levels consistent with the levels.
Some of which we observed efficacy and absolutely clinical studies.
We're now positioned to move of PTC 857 forward the phase 2.
Stuart activity at 15, lipoxygenase PTC 5.7 targets of the pathway of oxidative stress and inclination known as fair of ptosis pathway key to CNS disease pathogenesis.
Matt: Our preclinical program has demonstrated that PTC 857 provides potent protection against oxidative stress and inflammation-based cell injury and death in a series of CNS disease in vitro and in vivo tests. Turning now to our PKU program, we are on schedule to initiate our Phase 3 Registration-Directed Trial, the Affinity Study, with PTC 923 this quarter. As a reminder, AFFINITY is a double-blind, placebo-controlled study with a run-in phase to identify subjects who respond to PTC 923 treatment.
S Parkinson's disease and other Neurodegenerative disorders.
Our preclinical program has demonstrated that PTC 857 provides potent protection against oxidative stress of inflammation based cell injury and debt and a series of CNS disease in vitro and in vivo test systems.
Turning now to our PKU program, we are on schedule to initiate our phase III registration directed trial. The affinity study with PTC 93 this quarter.
As a reminder, affinity the double blind placebo controlled study with a run in phase to identify subjects, who respond to PTC 90 twos to retreat.
He's responders will then be randomized to receive either PTC 93 or placebo for 6 weeks.
Matt: These responders will then be randomized to receive either PTC923 or placebo for six weeks. This approach of enriching the study population with responders increases the probability of success of the trial. Following the FFTC study, all subjects will be eligible to enroll in a long-term open-label, We plan to have data from the efficacy trial in the fourth quarter of 2020. Turning now to our gene therapy platform, as Stu noted, the third cannula surgery in support of the AADC BLA submission has been completed.
This approach of enriching the study population with responders increases the probability of success of the trial.
Following on the efficacy study all subjects will be eligible to enroll in a long term open label.
The extension study.
The plan to have data from the efficacy trial in the fourth quarter of 2022.
Turning now to our gene therapy platform as Steve noted the third cannula surgery in support of the E. A D. C. BLA submission has been completed.
To align with the FDA on the data package and.
Matt: We plan to align with the FDA on the data package and then submit the DLA by the end of the year. As a reminder, the surgeries were conducted to gain experience with the intended commercial cannula for delivering our gene therapy products. One of the innovative aspects of our AADC gene therapy program is that the gene therapy product is delivered directly to the patient, to the area of the brain key to disease pathology.
And then to submit the BLA by the end of the year.
As a reminder, the surgeries were conducted to gain experience with the intended commercial cannula in delivering our gene therapy product 1.
1 of the intervenors of aspects of our AAV gene therapy program is that the gene therapy product is delivered directly to the pertain.
The area of the brain key to disease pathology.
Where did you achieve the direct delivery into the brain tissue neurosurgeons use of stereotactic surgical procedure that relies on an MRI based Google map that provides a direct path from the surgeon to safely reached the quick payment to deliver on the junior debt.
Matt: In order to achieve this direct delivery into the brain tissue, neurosurgeons use a stereotech surgical procedure that relies on an MRI-based Google map that provides a direct path for the surgeon to safely reach the gluteus muscle to deliver the tissue. Let me now provide a quick update on Embodistat, previously PTC 299, currently in a phase 2-3 trial for COVID-19. The Fight Night.
Let me now provide a quick update on M vote of staff previously PTC to knock on currently in a phase 2.3 trial for COVID-19 the.
19 study.
Enrollment is ongoing in this trial and we expect the study to be completed by the end of this year.
Matt: Enrollment is ongoing in this trial, and we expect this study to be completed by the end of the year. As a reminder, Embodistat is also being studied in an ongoing trial in patients with acute myeloid leukemia. Finally, I would like to remind you of our ongoing placebo-controlled trial with TransLarna for Duchenne muscular dystrophy, study 041.
As a reminder, and vote of set is also being studied in ongoing trial in patients.
With the acute myeloid leukemia.
Finally, I would like to remind you of our ongoing placebo controlled trial with trans lineup of Duchenne muscular dystrophy study of <unk> 4.1.
This global study to the 72 week randomized placebo controlled trial that incorporates many of the key learnings we have made from a previous DMD trials.
Matt: This global study is a 72-week randomized placebo-controlled trial that incorporates many of the key learnings we have made from our previous DMD trials. This study is fully enrolled, and we expect to have results in Q3 2020. In summary, we are continuing to move our development programs forward with many important milestones in the near future. I will now turn the call over to Eric for an update on our commercial business. Thanks, Matt.
The studies.
He is fully enrolled and we expect to have results in Q3 of 2022.
In summary, we are continuing to move our development programs forward with many important milestones in the near future.
I will now turn the call over to Erik for an update on our commercial business.
Eric.
Thanks, Matt once again.
I'm extremely proud of the strong execution from our global customer facing team and the continued remarkable growth of our global DMD franchise.
Eric: Once again, I'm extremely proud of the strong execution from our global customer-facing team and the continued remarkable growth of our global DMV franchise. With our keen focus on patients, our team was instrumental in delivering another highly successful quarter for commercial revenue. We are seeing incredible progress in our DMV franchise with year-over-year growth in both Enflava and TransLarna, resulting in a 36% growth for the franchise. New patient starts, continued high adherence, and fewer discontinuations have sustained the growth of the plaza.
With our keen focus on patients our team was instrumental in delivering another highly successful quarter for commercial revenue.
We are seeing incredible.
Progress in our DMD franchise with year over year growth in <unk>.
Both the plaza entrance learn of resulting in a 36% growth for the franchise.
New patient starts continue the Hyatt here.
And few of discontinuation of sustain the growth of the Plaza.
In this quarter.
We achieved $49 million in revenue.
Eric: In this quarter, we achieved $49 million in revenue, which is a 36% increase over the second quarter of 2020. Strong Execution, supported by new data recently presented by Dr. Craig McDonald at the PPMD meeting, continues to support clinical differentiation over prednisone and is helping drive new prescriptions from patient switches. Turning to TransWire.
Which is a 36% increase over the second quarter of 2020.
Strong execution supported by new data recently presented by Dr. Craig Mcdonald at the P. P. M. D meeting continues to support clinical differentiation over prednisone.
<unk> is helping drive new prescriptions from patient switches.
Turning to trans border.
We achieved $53 million in revenue this quarter.
Eric: We achieved $53 million in revenue this quarter, a 36% growth over the second quarter of 2020. This sustained performance was driven by growth due to expansion of the patient base, continued high compliance, and broader access to the existing geography as well as continued geographic expansion.
A 36% growth over the second quarter.
Of 2020.
The sustained perform.
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By growth due to expansion of the patient base.
Continued high compliance.
And broader access of the existing geographies as well as continued geographic expansion.
That's an example of geographic expansion following the approval of trends, Florida.
Eric: As an example of geographic expansion, following the approval of TransLarna in Russia, we are pleased to announce that we have successfully launched, and patients are now receiving treatment. The launch in Russia and continued growth in other key markets have been one of the major drivers for revenue growth in the second quarter of 2021. Ongoing geographical expansion in Central and Eastern Europe, Latin America, the Middle East, and Asia Pacific continues to be a focus for us, including expanding our footprint and infrastructure in additional markets such as Japan and Mexico.
And Russia we.
We are pleased to announce that we have successfully launched and patients are now receiving treatment.
The launch in Russia, and continued growth in other key markets had been 1 of the major drivers for revenue growth in the second quarter of 2021.
Ongoing geographical expansion in central and eastern.
In Europe, Latin America, the Middle East and Asia Pacific continues to be of focus for us, including expanding our footprint and infrastructure in additional markets, such as Japan and Mexico.
We are making continued progress with reimbursement per trends 1 of them and we're pleased and extending.
Eric: We are making continued progress with reimbursement for TransWarner, and we are pleased to have extended the Managed Access Agreement in English. In Latin America, we continue to see increases in newly diagnosed DMD patients and are making good progress towards securing a group purchase order for TransLana in Brazil in the second half of 2021 to treat both new and existing DMD patients. Now, turning to Teixeti and Muehlebra, disease awareness and patient identification continue to be the focus in Latin America, and our teams have made substantial progress despite the ongoing COVID-19 challenges. In Brazil, our discussion on pricing for tech settings continues.
The managed access agreement in England.
In Latin America, we continue to see increases in newly diagnose DMD patients.
And are making good progress towards securing the group purchase order for Translarna in Brazil in the second half of 2021 to treat both new and existing of DMD patients.
Now turning to Chegg study and way Libre, the disease awareness and patient identification continues to be the focus of Latin America and our teams have made substantial progress. Despite the ongoing COVID-19 challenges in the region.
In Brazil, our discussion on pricing protect study continues during.
During the process.
We continue to provide medical education genetic testing and patient program support to the Tech city available in multiple countries within Latin America through early access programs to bring this important treatment for H ATR amyloidosis patients.
Eric: During this process, we continue to provide medical education, genetic testing, and patient program support to make TxETI available in multiple countries within Latin America through early access programs to bring this important treatment for HHETR amyloidosis patients to patients. We are pleased that we now have some of the first patients benefiting from treatment with Waylibra in Latin America through Early Access Pathways. We're preparing for a launch in Brazil, but due to COVID delays in Ibiza.
We are pleased that.
At the.
I'll have some of the first patients benefiting from the treatment with way Libre in Latin America through early access pathways.
We're preparing for a launch in Brazil, however, due to COVID-19 delays at visa.
The registration is now anticipated in Q4.
Eric: Waiver registration is now anticipated in Q4. NVSA has announced the establishment of a task force to address the backlog of pending applications with priority for rare disease applications. I will now touch on the preparation for PTC's first gene therapy law. As a reminder, PTC AADC is a transformative gene therapy that has the potential to produce meaningful changes in AADC deficiency patients. Preparations are progressing well, and we anticipate the launch to occur in Europe shortly after final EMA approval.
We know the visa has announced the establishment of the task force to address the backlog of pending applications with a priority for rare disease applications.
I will now touch on the preparation for Ptc's first gene therapy launch as a reminder, PTC a D C.
The transformative gene therapy that has the potential to produce meaningful changes in a agency deficiency patients.
Preparations are progressing well and we anticipate the launch to occur in Europe. Shortly after the final E M a approval.
PTC.
<unk> continues to accelerate patient screening activities with over 100 at home and saliva based on genetic testing programs in over 20 countries initiated an enriched high risk populations.
Eric: PTC continues to accelerate patient screening activities with over 100 at-home and saliva-based genetic testing programs in over 20 countries initiated in enriched high-risk populations. Significant progress has been made with the identification and preparation of expert pediatric neurological centers of excellence throughout the U.S., the EU, and Latin America to ensure treatment center readiness at the time of launch. And we remain confident that we will achieve our goal of 300 patients identified globally by launch.
Significant profit progress has been made with the identification and preparation of extra.
Expert pediatric neurological centers of excellence throughout the U S. The EU and Latin America to ensure treatment center readiness at the time of launch and we remain confident to achieve our goal of 300 patients identified globally.
Launch.
We generated another strong.
Strong and sustained performance of the Q2 and I continue to take great pride in our accomplishments from the global customer facing teams and their ability to flawlessly execute against their strategic priorities with that.
Eric: We generated another strong and sustained performance in Q2, and I continue to take great pride in our accomplishments by global customer-facing teams and their ability to flawlessly execute against their strategic priorities. I am pleased to announce that PTC is raising our 2021 revenue guidance to $370 to $390 million. I will now turn the call over to Emily for a financial update.
I'm pleased to announce the PTC is raising our 2021revenue.
Yes.
370 to 300 of $90 million.
I will now turn the call over to heavily for a financial update Emily.
Thanks, Jack and the second quarter of 2021, we continued to see strong commercial performance and demonstrated progress across our pipeline.
Emily: Thanks, Eric. In the second quarter of 2021, we continued to see strong commercial performance and demonstrated progress across our pipeline. We remain in a healthy financial position with a robust cash balance and another year-over-year increase in revenue from the BNB franchise. We have been working strategically to advance key platforms and look forward to a number of upcoming milestones from our pipeline. In light of the consistent strong performance of TransLarna and M-PLAZA to date, we are pleased to raise revenue guidance for the DMD franchise for 2021 from the original 2021 revenue guidance of $355 to $375 million.
Got you remain in the healthy financial position with a robust cash balance and another year over year increase from revenue from the DMD franchise.
We have been working strategically to advance key platforms and look forward to a number of upcoming milestones from our pipeline.
In light of the consistent strong performance of Translarna and <unk> Plaza.
We are pleased to raise revenue guidance for the DMD franchise for 2021 to $370 million to $390 million from the original 2021 revenue guidance of $3.55 million to $375 million.
The press release issued earlier this afternoon summarizes the details of our second quarter of 2021 financial results.
Emily: The press release issued earlier this afternoon summarizes the details of our second quarter 2021 financial results. I will take a few minutes now to review these financial results. Please refer to the press release for additional details. Beginning with the top line results, revenues were $117 million for the second quarter of 2021, a 55% increase over the second quarter of 2020. This revenue includes $103 million in net product sales and $14 million in royalty revenue from our Partner Diversity Program.
I will take a few minutes now to review these financial results. Please refer to the press release for additional details.
Beginning with the top line results revenues were $117 million for the second quarter of 2021 of 55 per cent increase over the second quarter of 2020.
This revenue includes the 103 million of net product.
Think of and $14 million in royalty revenue from our partner that Brinci.
The program.
Turning now to more detail on the success of the DMD franchise.
Emily: Turning now to more detail on the success of the DMD franchise, TransVarna net product sales were $53 million, compared to $39 million in the second quarter of 2020. A key driver of this growth has been geographic expansion, particularly in Russia and the Central and Eastern Europe, Middle East, and North Africa regions.
And then final net product sales were 53 million compared to 39 million on the second quarter of 2020.
A key driver of this growth has.
Has been through geographic expansion, particularly in Russia, and the central and Eastern Europe, Middle East and North Africa region.
The Plaza net product revenue for this quarter was $49 million as compared to 36 million in the second quarter of 2020.
Emily: MFLAZA Net Product Revenue for this quarter was $49 million, as compared to $36 million in the second quarter of 2020.
Moving on to an update on average our partner Roche has reported year to.
Emily: Moving on to an update on Eversbee, our partner Roche has reported year-
Net sales of approximately 243 million Swiss francs, which is approximately 265 million U S dollars.
Emily: Here is a list of the year-to-date sales of approximately 243 million Swiss francs.
Emily: 23 million Swiss francs, which is approximately 265 million US dollars. As a reminder, in exchange for $650 million in upfront cash added to our balance sheet, PTC also retains approximately 57% of Everest's royalties until Royalty Pharma receives a return of $1.3 billion. After that, 100% of the royalties revert back to TTC. As part of this royalty monetization transaction, PTC also retains sales and regulatory-based cash milestones.
As a reminder, in exchange for 650 million upfront cash added to our balance sheet. PTC also retains approximately 50% 7% of that brinci royalties until royalty.
Realty were part of my receives a return of $1.3 billion.
After which a 100 per cent of the royalties revert back to PTC.
As part of this royalty monetization transaction PTC also retained sales and regulatory based cash milestones.
Following the approval of the bridge the in Japan this quarter.
So we anticipate the near term $10 million milestone payment upon the first commercial Japanese sales.
Emily: Following the approval of BRISBEE in Japan this quarter, we anticipate a near-term revenue of $10 million.
Non-GAAP R&D expenses were 112 million for the second quarter of 2021, excluding $13.4 million of noncash stock based compensation expense.
Emily: We anticipate a near-term $10 million milestone payment upon the first commercial Japanese sale.
Compared to $168 million for the second quarter of 2020, excluding $8.6 million of noncash stock based compensation expense.
Emily: Non-GAAP R&D expenses were $112 million for the
Emily: Thank you for joining us today. The relative decrease in research and development expense is primarily related to one-time charges in the second quarter of 2020 of $53.6 million for our SAMHSA merger, as well as $41.2 million for our Commercial Manufacturing Service Agreement with MassBiological. Non-GAAP SG&A expenses were $56.6 million for the second quarter of 2021, excluding $12.3 million in non-cash stock-based compensation expense, compared to $45.3 million for the second quarter of 2020, excluding $8.3 million in non-cash stock-based compensation expense. Cash, Cash Equivalents, and Marketable Securities totaled $947.1 million as of June 30, 2021, compared to $1.1 billion as of December 31, 2020.
The relative decrease in research and development expense was primarily related to 1 time charges in the second quarter of 2020 of $53.6 million for our sense of merger as well.
Quarter, $1.2 million for commercial manufacturing service agreement with mass biologics.
Non-GAAP SG&A expenses were $56.6 million for the second quarter of 2021, excluding $12.3 million of noncash stock based compensation expense compared to $45.3 for the second quarter of 2020.
It's <unk> 40, excluding $8.3 million of noncash stock based compensation expense.
Cash cash equivalents and marketable securities totaled $947.1 million as of June 30 of 2021 compared to $1.1 billion as of December 31.2020.
I'll now turn the call over to the operator for Q&A operator.
Operator: I'll now turn the call over to the operator for Q&A. Operator. Thank you. Ladies and gentlemen, as a reminder to ask...
Okay.
Thank you, ladies and gentlemen, as a reminder to ask the question you would need the press Star then 1 on your telephone.
Operator: If you have a question, you will need to press star and then 1 on your telephone. To withdraw your question, press the pound key. Again, that's star one to ask the question. Please stand by while we compile the Q&A roster.
To withdraw your question press the pound key.
Thats Star 1 to ask the question please.
Please standby, while we compile the Q&A roster.
Yeah.
The first question comes from the line of Eric Joseph with J P. Morgan Your line.
Eric William Joseph: Our first question comes from the line of Eric Joseph with J.P. Morgan.
Line is open.
Eric William Joseph: JPMorgan, your line is open. Good evening.
Good evening, thanks for taking the question.
Eric William Joseph: Thanks for taking the question. A nice quarter. Just on the DMT franchise performance, with guidance now raised here, if we're looking at the midpoint, that actually seems to imply a flat to down trajectory for the second half. So I'm just wondering if you could kind of talk us through any risks that you're anticipating with respect to ongoing performance with either TransLana or Inflaja, and wondering whether these second quarter results reflect any advanced purchasing or stocking. Could I have a follow-up? Yes, thanks, Eric, for the call. Eric, why don't you take this? Sure, Eric.
Nice quarter.
Just on the DMD franchise performance.
With guidance now raised here, we're looking at the mid.
Midpoint, it actually to certify.
The slots of down trajectory for the second half. So I was just wondering if you could kind of talk us through any risks that youre anticipating with respect to.
The ongoing performance of either Translarna or the.
The <unk>.
Wondering whether the second quarter results reflect any.
The purchasing of restocking.
Follow up.
Yeah, Thanks for the call.
Eric where 2 of them.
Okay.
Sure Eric.
The first of all I think we got it.
Eric: You know, first of all, I mean, we had a terrific Q2. We had $53 million in sales for TransLarna. That's a 36% increase over last year. And within PLAZA, identically 36% growth. We had $49 million in revenue in the quarter.
Terrific.
You too.
We had 53 million.
The sales for Translarna net 36% increase over last year. It would imply the organically 36% growth, we had $49 million of revenue in the quarter.
I think when you look at our revised guidance.
Eric: I think when you look at our revised guidance, I think our guidance right now reflects that we're growing in all major markets. We're very proud of the work that the European team has done after seven years, especially in Northern and Southern Europe, where they have the largest base of patients. And we've been able to maintain that high base, a large base of patients with high compliance rates, minimizing dropouts. But where we're seeing growth right now is that really a lot of new patients are coming in from Russia, from Central and Eastern Europe, the Middle East, and our business in Latin America continues to be solid despite some of the COVID challenges that we have. And we expect, right now, orders in Latin America, and particularly Brazil, significant orders, which you already know can be somewhat lumpy.
Our guidance right now reflects that we're growing in all major markets.
We're very proud of the the work that the European team has done on after 7 years, especially northern and southern Europe, where they have the largest base of patients and we've been able to maintain that high base large base of patients with high compliance rates minimizing drop out, but where we're seeing growth right now.
It was really.
A lot of the new patients are coming in from Russia from Central and Eastern Europe, Middle East and our business in Latin America continues to be to be solid. Despite some of the COVID-19 challenges that we have and we expect.
Now orders in Latin America, particularly Brazil significant orders, which you.
You already know it can be somewhat lumpy, we anticipate those to happen in the second half of the year.
Eric: We anticipate that these things will happen in the second half of the year. So, overall, I think we're very confident. We have continued strong growth at Transmarna. On the emploza front, we had one of our best quarters ever, and we continue to see new patient growth. We also see that the compliance with emploza is extremely high, and more importantly, that the data that's being generated now, new data, real-world data, and switching data, we're seeing not only new patients, but we're seeing an increased amount of patients that are actually switching from prednisone to emploza, and that's really a very important sign.
So I mean overall I think we're very confident we have.
<unk> continued growth of the Trans Florida on the Plaza front.
1 of our best quarters ever and we continue to see new patient growth.
You'll see that the compliance within Plaza is extremely high and more importantly debt.
The data that's being generated net new data.
Real World data and switching data and we're seeing not only new patients, but we're seeing an increased amount of patients that are actually switching.
From prednisone.
Zone, 2 in Florida, and Thats really a very important side. So overall I think our guidance.
Eric: So, overall, I think our guidance, where we're looking at right now, is very strong, continued performance. It would be, right now, on the upper end, we'd be at least about 17% increase year over year, and that's pretty in line with what we think we can achieve, and the business right now has a good tail.
Where we're looking at right now is a very strong continued performance of it would be right now on the upper end would be at least about 17% increase year over year and that's pretty in line with what we think.
We can achieve.
We also the end.
In the business right now has a good tailwind.
Eric: Okay, great. And just a second question on and notice that the FITE-19 trial is focusing on hospitalized patients, but I'm just trying to get a sense of how you think about the market opportunity in view here, assuming success. Do you see potential for its use in the outpatient setting? Do you have the regulatory flexibility to do that? Or do you need to conduct a separate trial for outpatient use? Thanks. Yeah, thanks.
Okay, Great and just second question on in both the stat.
The price 19 trial is focusing hospitalized patients, but I'm just trying to get a sense of.
How are you thinking about the market opportunity is huge you're assuming.
The success do you see potential for its use of the outpatient setting.
The regulatory flexibility to do that.
Or do you need to conduct a separate trial for efficiencies.
Yeah, I think thanks for that question is on pause.
Particularly we're excited about the sister of money.
Stuart Peltz: Thanks for that question. And particularly, we're excited about this just to remind everybody that PTC 299 is a small molecule. And that it certainly can be used in the outpatient setting, right? So we think right now we're doing a hospital trial, but it certainly could be used. I think it has the advantage in that it's a dual mechanism. And that is because, first of all, it's a cellular mechanism, so it won't have the issue of, we don't anticipate as much of an issue with the SARS-CoV-2 mutating, and it targets the DH or DH cellular end.
Everybody the.
The PTC 299 of them.
Oral small molecule.
And so it certainly can be used in the outpatient.
Saturday right. So we think right now we're doing the hospital trial, but certainly cause the younger so I figured out of the advantage.
That is the dual mechanism and the.
That is.
Net.
Because of its mechanism of first of all.
Cellular mechanism. So it won't have the issue. So we don't anticipate as much of an issue with the Sars Covid 2 <unk>.
The U K.
Targets the D H O G H.
Cellular items on it.
The second of all I think by targeting book.
Stuart Peltz: And second of all, I think by targeting this, well, it's less likely to elicit drug resistance. So we, so on the whole, we think that this will certainly have a possibility in the outpatient setting, and we'll have to discuss with the FDA based on the results from the current trial. If successful, if and when it is successful, how can we use it in both the in-hospital as well as the patient?
The.
Less likelihood of illicit drug.
The resistance of the consequence of that.
So we sort.
So on the whole we think that.
This will certainly have a possibility in the outpatient setting and we'll have to discuss with the FDA based on the results from.
The current trial, if successful if and when successful how can we use it in both of the <unk>.
In the hospital as well as patient.
So we're certainly seeing.
I think that it has the capabilities of they use in both of them. It's simple to take you can get it you know obviously you get a prescription of and you can take it.
Stuart Peltz: So we're certainly seeing that it has the capability to be used in both, and it's simple to take; you can get it, you know, obviously you get a prescription, and you can take it as soon as you get it. Okay. Appreciate that. Thanks for taking the questions.
As soon as you get.
Get COVID-19.
Okay got it I appreciate that.
Thanks for taking the questions.
Thank you.
Thank you.
Unknown Attendee: Our next question comes from the line of Alethea Young with Cantor Fitzgerald. Your line is open. Hi, congratulations on all the progress. This is Nino. I'm from India, and thanks for taking the question. We were wondering for the Huntington's update at the end of the year if you could just share how much and what information we should get or expect around CSF.
Our next question comes from the line of Alicia Young with the cash.
From it's Gerald you line is open.
Yeah.
Hi, congratulations on all the progress of this is neena on kind of again, thanks for taking the question.
We were wondering for the the Huntington to up the end of year, if you kind of share how much and what information we should get our background CSS.
Thanks.
Sure.
Matt: Thanks. Sure. Matt, do you want to take this?
Matthew on the Tusa.
Yes, sure. So as we've said before the the phase 1 study the the key objective of that study was the demonstrated dose dependent LOE range of Huntington mrna and protein in peripheral blood cells for and a unique opportunity with an oral.
Matt: Yeah, sure. So as we've said before, the phase one study, the key objective of that study was to demonstrate dose-dependent lowering of Huntington mRNA and protein in peripheral blood cells. We're in a unique opportunity with an oral molecule that broadly distributes through the body and through the brain, where we have a ratio of lowering in peripheral blood cells of one to one with cells inside the brain. So what we're able to do is look at blood cells.
Oral molecule that broadly bias of distributors in the body into the brain, where we have a ratio of lowering in the peripheral blood cells of 1 to 1 with cells inside the range.
So what we're able to do is able to look at blood cells.
Peripherally and get a read on what's going on in the brain and that's really a function of 1 the bio distribution of all.
Matt: Peripherally, and get a read on what's going on in the brain, and that's really a function of one, the biodistribution molecule, and two, the fact that it is an oral molecule that's been designed, not the efflux from the CNS, and really penetrate all regions of the brain equally, which obviously is incredibly important in Huntington's, which is a total brain, And so that's what we were able to show so far with the data we've read out, and that does to the lowering of mRNA in peripheral blood cells in both the SED and MAD cohorts. And the CSF cohort we referred to is a pharmacology cohort.
2 of the fact that it is an oral molecule that's been designed that eplex from the CNS and really penetrate all regions of the brain equally which obviously is incredibly important in huntington's, which has a total of brain disease.
And so that's what we were able to show so far with the day, we brought out of that dose to pay debt.
Lowering of mrna in the peripheral blood cells on both.
Also on C D and that may be cohorts and the CSF cohort. We referred to is the pharmacology, what we're going to look at in the CSF of healthy volunteers is making sure we get Inc.
Matt: What we're going to look at in the CSF and Healthy Volunteers is making sure we get the bio-distribution to the CNS that we anticipate based on all the work we've done before. One key element of the design of this molecule was to ensure not only does it cross the blood-brain barrier but that it doesn't get efflux. That means once it gets across the blood-brain barrier, it stays in. And that's incredibly important for its biodistribution throughout all regions of the brain.
The bio distribution.
Mission to the CNS debt, we anticipate based on all of the work we've done before 1 key element of the design of this molecule.
The address to ensure not only just cross the blood brain barrier and that it doesn't get EPS. So that means from tickets across the blood brain barrier. It stays in and that's incredibly important for its 5 distribution throughout all regions of the brain or the way, we can tell whether or not that's happening is by measuring drug levels in the CNS in the CSF, specifically and comparing those levels to the peripheral.
Matt: Well, the way we can tell whether or not that's happening is by measuring drug levels in the CNS, in the CSF specifically, and comparing those levels to peripheral plasma levels. That's exactly the readout that we'll be getting from the CSF cohort, lining up the levels of drug in the plasma with the levels of drug in the CSF and being able to check that box that we're getting the desired end design. CNS penetration.
I'll kill the plasma levels. So that's exactly the readout that we'll be getting from the CSS copel lining up the the levels of drug in the plasma with the levels of drug in the CSS and being able to check that box that we're getting the desired and design.
Yes.
Yet CNS penetration and so specifically you'll be getting.
Matt: Specifically, you'll be getting a readout of drug levels in the CSF and being able to check that key box that we're getting the biodistribution, and lack of e-flux that we've seen in pre-clinical studies in animal models, and that's where the key design features are.
The readout of plot of drug levels on the CSS and being able to check that key box that we're getting the the bio distribution of lack of influx debt.
We've seen in the preclinical studies and in the animal models, where the key design feature of the market.
Okay.
Yeah.
Thank you.
Our next question comes from the line of Tuesday Ahmad with Bank of America. Your line is open.
Tazeen Ahmad: Our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is open. Hi, good afternoon.
Hi, good afternoon. Thanks, so much for taking my questions guys.
Tazeen Ahmad: Thanks so much for taking my questions, guys. I just have a couple. One on AADC. This is a program where I think you guys have been engaged in patient finding efforts for a while. It's been a few quarters since we've gotten an update on how many patients you've found. I think the last count was somewhere in the 200s. I was curious if you have any updated numbers on the addressable patient population that you could identify today. And then I have a follow-up.
I just have a couple of them 1 on a a D C.
This is the program, where I think you guys have been engaged in patient finding efforts for a while it's been a few quarters since we've gotten an update on how many patients seems found I think the last count with somewhere in the 200 was curious if you have any updated numbers on the addressable patient population that you could identify.
And then I have on all up.
Okay, yeah. Thanks.
Quick question on it.
Eric: Okay, yeah, thanks for the question. Eric, do you want to take it?
Are you on the ticket.
Yeah, you know right now we're still doing a lot of work as I mentioned earlier.
Eric: Yeah, Tazeen, you know, right now, we're still doing a lot of work. As I mentioned earlier, our plans are really continuing to aggressively look at and pursue patient finding You know, we're not at this point in time; we're not going to be prepared to provide numbers of patients, but we're well on track right now to achieving our goal, which is to have 300 addressable patients between now and the time when we have our first launch.
Our plans are really continuing to aggressively look at pursuing patient finding.
Today.
Not at this point of time, we're not gonna be compared the required number of patients per well on track right now to achieving our goal which is to have 300 addressable patients.
Between now and the time when we have our per Sloshed out we're anticipating our launch.
Eric: Now, we're anticipating our launch, the first country launch to be in Germany, and that would be following EMEA approval, and at that time, we'd be providing the number of patients. But you have to be really, really, you have to understand that this is an ultra rare disease, and what we've done is we've really cast the net pretty widely now. So we have 100 programs right now where we have been screening patients in very high-risk populations, particularly in cerebral palsy and epilepsy centers, and we've spread our net geographically to over 20 countries.
The first country launch will be in Germany, and that would be.
Following the EMEA approval and at that time, we'll be providing the number of patients.
But you have to be really really you have to understand that this is an ultra rare disease and what we've done is we've really cast the net pretty widely now. So we have 100 programs right now where we have been screening patients in the very high risk population.
Particularly like on the cerebral palsy epilepsy centers, the recasting of our that's geographically to over 20 countries and those 20 countries really represents.
Eric: And those 20 countries really represent areas where we can get access and reimbursement. But keep in mind, when we announce the number of patients at the time of launch, that would be the number of patients globally, and then, of course, that will be sequenced according to market access and reimbursement amongst various countries in Europe and in early access programs across the globe. So we're really focusing on that. We're focusing on not only just patient finding, but making sure that our centers are ready, and we have centers right now that have, as Matt said, treated patients in the US, in Europe, in Asia, and we're really expanding the, if you will, pediatric neurological centers of excellence. So we make sure that when we have these patients, they'll be able to be treated as quickly as possible. Okay.
Areas, where we can get access in reimbursement, but keep in mind, when we announced the number of patients at the time of launch that would be the number of patients globally, and then of course debt.
That will be sequenced according to market access and reimbursement amongst various countries in Europe and the early access programs across the book, So really focusing on that we're focusing on not only just patient finding but making sure that our centers are ready and we have centers right now as.
It's Matt.
<unk>, who have treated patients in the U S and Europe.
And Asia, and we're really expanding the if you will the pediatric neurological centers of excellence to make sure that when we have these patients there'll be able to be treated as quickly as possible.
Okay and.
Some of your total addressable population that you're thinking because that's I think of your last guidance on somewhere between 5 and 6000 patients.
Tazeen Ahmad: Okay, and in terms of the total addressable population that you think exists, I think your last guidance was somewhere between 5,000 and 6,000 patients. Is that still your view?
Is that still your view.
Okay.
Oh sure.
We currently the.
Eric: We currently, yes, our current, what we've seen not only in the published literature and the work that we've done in terms of screening programs, particularly in the rich population, suggests that that is a sort of global number. Now remember, this treatment is not sort of a simple product that you're going to use like a tablet, a wall, or even an infusion. So this is going to require a stereotactic approach, surgery, and follow-up.
Yes, our current the what.
We see not only.
Only in the published literature of the work that we've done in terms of screening programs, particularly in rich population suggested that that is the sort of global number I remember this treatment is not sort of a simple <unk>.
Product that youre going to use like a tablet on the hall or even on an infusion. So is this the requires stereotype.
In terms of approach surgery and follow up so the intervention of the treatment of of the patient is going to be slightly more complicated than sort of your average treatment that debt we would do so.
Eric: So the intervention and the treatment of the patient is going to be slightly more complicated than sort of your average treatment that we would do. So in terms of how and what we believe the number of patients that exist, I think it's incredibly important to know that we have made important strides in finding these patients through these genetic testing programs. The pinpoint program in the U.S. is finding patients, the saliva programs that we're using are simple and easy to use, and we're finding these patients in many of the countries where we know that gene therapies are currently being reimbursed, and that's really important.
In terms of how and what we believe the number of patients that exist.
Credibly important to know that we have made.
<unk>.
[noise] strides in finding these patients through the genetic testing program. The pinpoint program in the U S. In spite of inflation saliva programs that were using are simple and easy to use and we're finding patients and many of the countries, where we know the gene therapies are currently being reimbursed and that's really important.
Okay.
Yeah.
Is there and where you know the beauty of we're finding them everywhere as well in many different countries. So I think we're you know we're in pretty good shape that still gives us the confidence that there's about 5000 patients there.
Eric: Okay, so there are thousands there. And we're, you know, the beauty is that we're finding them everywhere as well in many different countries. So I think we're, you know, we're in pretty good shape. That still gives us the confidence that there are about 5000 patients there.
Okay. Thank you and then if I could squeeze 1 in on our on time.
On June 10th just to clarify.
Aerophyte are you planning on showing them knocked down from wild types by the end of this year.
Tazeen Ahmad: Okay, thank you. And then if I could squeeze one in on Huntington's. Just to clarify, are you planning on showing Knockdown for Wild Types at the end of this year?
So in the wood, that's where we're looking at both we.
We don't discriminate between wild type of new E. So yeah, you'll be seeing the the the overall of the levels reflect the overall levels of the R&D.
Stuart Peltz: So in the, we're looking at both. We don't discriminate between wild-type and mutant, so yeah, you'll be seeing the levels reflect the overall levels of the RNA that we see since it's both of them, both wild-type and mutant are seen, so you'll get that as well as the protein level reduction from both of them.
But we see some sort of both of them both wild type of things. So you will you get that as well as the protein level of reduction from both of them.
Okay, but will you be specifically high so I think with the wild type knockdown of.
I think it will be we'll be showing you know, we'll be able to say what.
With the wild type of knockdown of <unk>.
On the over the sort of differentiation between the true.
Stuart Peltz: Okay, but will you be specifically highlighting what the wild type knockdown is?
In that sense.
Okay got it.
The 952.
Stuart Peltz: I think we'll be showing, yeah, we'll be able to say what the wild type knockdown is based on the OVA. There's no differentiation between the two, in that sense. Okay, got it. 49 to 60. So it's a one to one ratio. Okay.
The 1 to 1 ratio.
Okay got it thank you.
Okay.
Thank you.
Our next question.
The comes from the line of Brian Abrams with RBC capital markets.
Line is open.
Hi, This is Steve on for Brian Thanks for taking on a question another 1 on Huntington's.
Curious what is known about how the neuron adapts to the accumulation of mutant Huntington overtime and given the data from animal models of preclinical models that might tell us whether sort.
Brian Corey Abrahams: Okay, got it. Thank you. Thank you. Our next question comes from the line of Brian Abrahams with RBC Capital Markets.
Depletion of the mutant protein could cause.
On.
On the inflammation or just regulated protein turnover.
We don't have a baby.
Stuart Peltz: We don't have any. I think, you know, there's been several studies that show, in terms of clinical, Benefit Riding Animal Models That Show the Lowering of Htt Results in Improvements in Animals. I think I don't think you have a rapid reduction in that sense is causing any sort of unusual consequence that I know of it, and the Animal Studies.
You.
You know you know.
I think you know theres been several studies that show in terms.
The rapid growth.
Benefit right in animal models.
So the the lowering the lowering of H T T, resulting in improvements in the animals. So I think I don't think you have oh rapid reduction of that census, Crosby nuomi.
Sort of.
Unusual consequence that I know of at least.
Animal studies.
Thanks.
Peyton Bohnsack: Hi guys, this is Peyton Bohnsack for Joe. Thanks for taking my question and congrats on the strong quarter. I was wondering if you could provide a little more background on why ALS was chosen for PTC 857 instead of some of these other CNS disorders or neurodegenerative disorders and any timeline on when you'll release more details on the trial design. Thanks. Sure, so maybe I'll start and then pass it on to the next person. I think the...
Thank you.
Our next question comes from the line of Peyton the bonds that with Cowen Your line is open.
Hi.
Of the clinical the paying on for Joe. Thanks for taking my question and congrats on the strong quarter. I was wondering if you could provide a little more background on my AOS has chosen for PTC ATI 7 instead of some of these other CNS disorders, or neurodegenerative disorders, and any timeline on when Youll release more details on the trial design.
Sure So maybe I'll start.
Starting on passing them on from that.
I think the the.
The you know if you think about 85 of them in and of the whole bio E platform of knowing that really in terms of you know excess electrons that leads oxidative stress.
Stuart Peltz: So, you know, if you think about 857 and the whole BioE platform and know that really, in terms of, you know, excess electrons that lead to oxidative stress and turns on inflammation, aggregation, it's a key, so 85, the 15-lipoxygenase is a key mediator in this process. And then when you're, in a sense, when the system of stopping the end of electrons gets overwhelmed, this is sort of the emergency response system that ultimately turns on the inflammatory response to try and fix things, so it's a real problem that it gets turned on and doesn't get turned off.
And turns on the inflammation causes of aggregation is the key.
Alright got it Scott.
15 lipoxygenase is the key mediator in this process and then when when you're in the sense when the the system of Sopping up end of the electrons gets overwhelmed.
This is sort of the emergency response system the ultimately.
Turns on the inflammatory.
So on.
The trial and fixing so it's a real problem sort of gets turned on the doesn't get turned off but the.
I guess the important point is that can be used.
Stuart Peltz: But I guess the important point is that it can be used in a wide range of diseases; it happens in all of the neurodegenerative diseases, as well as many others. So you can go through multiple of them. And our notion was to look at a number of them. And maybe Matt will go through them.
And of why it happens in all of the neuro degenerative diseases as well as many other things. So you can go through of multiples of them on.
On our notion was the look at a number of them and maybe Matt will go through the.
And that's the idea of we will be doing that but once you go through rest of the why we're picking up.
Matt: You know, and that's the idea. We will be doing that. But Matt, why don't you go through why we're picking ALS as the first example? Yeah, sure, Stu.
<unk> is the first example.
Sure.
You mentioned the entire of preclinical program has been.
Matt: As Stu mentioned, the entire preclinical program has been based on the understanding that targeting 15-life oxygenase and its pathway of oxidative stress and inflammation is critical in a number of different neurodegenerative disease pathologies, including ALS, Parkinson's disease, and others. So what we've done is looked at a number of different in vivo and in vitro models of a number of different diseases and have been able to show strong efficacy across all of these models, some that are generic to neurodegenerative diseases and others that are disease specific.
Based on the understanding that target of 15 lipoxygenase kind of its pathway of oxidative stress in the inflammation.
Is critical in a number of different neurodegenerative disease pathology, so, including the loss, including Parkinson's disease and others. So what we've done is looked at a number of different in vivo and in vitro models of a number of different diseases and have been able the.
Show strong efficacy across all of these models some of that are generic charge and the CS and others that are disease specific.
So we arrived now with the phase 1 data in hand, and the ability to move the phase 2 and our selection of the starting first with ALS.
Matt: So we arrive now with phase one data in hand and the ability to move to phase two, and our selection of starting first with ALS is based on the fact that right now we have three months; we have toxicology studies to support three-month dosing. And when we think about neurodegenerative disease development, one of the key considerations is actually, one, having it, being able to dose it for long enough to see change, so the rate of progression of the disease, and then also being able to, of course, identify the right patients that are going to change over time in the trial so that you're able to show benefit.
And based on the fact that right now we have 3 months.
The strong Tox studies to support team on dosing and when we think about neuro degenerative disease development 1 of the key 2 of the key considerations actually are 1 of having.
Being able to dose for long enough to see change the rate of progression of the disease and then also being able to of course identify the right patients that we're gonna change overtime.
Of the trial, so that you're able to show benefit 1 of the key advantages of a L. S is at.
Matt: One of the key advantages of ALS is that Unfortunately, it's a rapidly progressive disease, and despite there being two approved therapies, there's still a significant unmet need. The disease is still rapidly progressive and fatal, with the majority of patients dying between 18 and 36 months following diagnosis.
Unfortunately, it's a rapidly progressive disease. Despite there being 2 of approved therapies, there's still a significant unmet need the diseases the rapidly progressive and fail with the majority of patients die of between 18 to 36 months following diagnosis, but over.
And of course prior to that ultimate.
The demise of the patients with ALS is a rapid decline in neurological function of muscular function in respiratory function all of which are already on the measurement.
Matt: But prior to that ultimate demise of the patient with ALS, there is a rapid decline in neurological function, neuromuscular function, and respiratory function, all of which are readily measurable. We also have an ALS, a validated endpoint, the ALS-FRS, which is known to change over a three-month period of time and allows us, based on the use of both the placebo group as well as robust natural history data, to show in a three-month treatment study with PTC-857 that we can have an impact on the disease. So what we have here is a disease in ALS where our preclinical work has been understood to explain the pathogenesis of the disease and the importance of our target pathway of the phenolipoxygenase in that disease.
Also having a loss of validated endpoint of the ALS FRS, which is known to change over.
2 months period of time and allows us based on use of both the placebo group as well as robust natural history data cable to show on a 3 month treatment studying the PTC 5.7 that we can have an impact on the disease. So what we have here is the disease and a loss of our preclinical work was understood about the pathogenesis the disease and the importance.
<unk> set our target pathway of 15 lipoxygenase in that disease, we have an opportunity of the 3 months study to show a treatment effect that can then inform a then.
Matt: We have an opportunity in a three-month study to show a treatment effect that can then form a definitive registration-directed study. So just to summarize, basically, where we are in terms of the toxicology program, having the three months of data complete and being able to do three months of dosing to be able to have an ALS and do this work. In that period of time, we can collect the necessary data to show the PKPD effect and then be able to move on to efficacy.
Definitive registration directed study.
So just to summarize basically the selection of the ALS is the first indications based on where we are in terms.
3.
Apology program being having a of 3 months of data complete and being able to do 3 months of dosing to be able to have an analyst day disease, where in that period of time, we can collect the necessary data to show PK PD effects, and then be able to move on to the efficacy. So right now we're in the process of.
The designing that trial, it's kind of on probably elements of the running phase to establish a baseline rate of progression of disease in at least the been the theme of treatment window of but we're still sorting out exactly tails on there'll be a placebo dose groups as well when he was very standard a lot of fans.
Matt: So right now, we're in the process of designing that trial. It's probably going to include elements of a run-in phase to establish a baseline rate of progression of disease and at least within the three-month treatment window, but we're still sorting out the exact details. There will be placebo and dose groups as well. We'll use very standard ALS endpoints. Obviously, I mentioned the validated ALS-FRS scale, which is a validated endpoint that has been used for approval previously, as well as other important biomarkers that can give us key indications of pharmacodynamic effects, particularly relevant to both the disease of ALS and the mechanism of action of PPC8.7. We plan to begin that trial in the first quarter of 2022, and we'll provide more details on the full study design Thank you; that was very helpful.
Obviously, I mentioned it without anything else FRS.
Of scale, which is a validated endpoint, which has been useful approval of previously as well as the other important biomarkers that the EBIT key indications of a pharmacodynamic effect, particularly out of particularly relevant to both the disease about layoffs and all of us in the mechanism of action of PTC outside of the.
The plan to begin that trial in the first quarter of 2020.
The 2 and we'll provide more details on the pulse of redesigning this is Randy.
That's very helpful.
We are.
Just on 1 more quick kind of follow on questions that you plan on.
Moving into other indications of we wait until this trial is done with the data.
Thanks.
Our goal will be this is I think it's more of a timing issue than anything else because of having.
Stuart Peltz: Will you plan on going into other indications or will you wait until this trial is done with the data? Our goal will be, this is, I think it's more of a timing issue than anything else because of, you know, having short versus long-term toxicology and we've always, I think we've said that the adult neurodegenerative indications were GPA, Parkinson's disease, and ALS. This is more of a matter of timing to get into that.
However, even short versus long term.
Toxicology and we've always I think we'd expect the.
The adult neuro of agenda of the certification.
The G P a park.
These loans.
This is more of a matter of timing to get into them.
Okay. Thank you that was very helpful.
Thank you.
Our next question comes from the line of Danielle Brill with Raymond James Your.
So Nelson.
Yeah.
Danielle Brill: Our next question comes from the line of Danielle Brill with Raymond James. Your line is open.
Hi, This is Alex on per Danielle. Thanks for taking the question I was hoping to see if you could provide any color on your plans for the $5.8 Huntington's phase II patient pool, we've been hearing from Kols of the patient pool should be of early stage Huntington's disease of possible to capture the benefit of what's feasible to address.
Alex: Hi, this is Alex. I'm here for Danielle.
Matt: Thanks for taking our question. I was looking to see if you could provide any color on your plans for 518 Huntington's Phase 2 patient pool. We've been hearing from KOLs that the patient pool should be as early stage Huntington's disease as possible to capture benefit. Is this feasible to address in Phase 2? And if not, could you share your thoughts on how you're approaching the enrollment criteria for the patient pool in the Phase 2 trial? Thanks.
Your line of phase 2 and if not could you share your thoughts on how you are approaching the enrollment criteria for the patient pool of phase II trial. Thanks.
Sure.
I'll make a general term announcements with the.
Obviously, the in any of these diseases.
In the neuromuscular.
Sales from the candidates where the.
Where do you feel with the always once you get it as early as possible.
But it still could be in the range of.
Stuart Peltz: Sure. I mean, I'll make a general statement now to answer that. You know, obviously, in any of these diseases that are either neuromuscular or neurodegenerative where you see a decline, you always want to get in as early as possible, but still, be in the range of while you're in early that there's some decline that you can measure, right, so that at the end of the day, it isn't, if you come in too early, the decline takes too long for a clinical trial. For Patient Population Choosing the Right Endpoint in the Range That You Think. It's very much like Goldilocks, right?
Well you're in the early that you that there is some decline that you can measure of right so that the.
The end of the day it doesn't come in too early.
The.
The decline takes too long for.
The clinical trial in terms of because they have to hit the right.
You shouldn't population choosing the right endpoint in the range of.
During the months like the Goldilocks right.
Too early is it doesn't help you on 2 late doesn't help you. So you have to find the right patient population.
And that's.
That's it.
A fair amount of of looking at the natural history and trying to define.
What's the right patient population the what's the right outcome for that particular population can you see it in the in the given.
Given the amount of time that you're going to do the experiment the drove high confidence in them to find the patients.
The.
Is the.
Cruising exclusion criteria with the gets you the patient population that you're kind of from confidence it will be declining. So that's the philosophy of what we're taking them.
Matt: Too early doesn't help you, and too late doesn't help you, so you have to find the right patient population. And that takes a fair amount of looking at the natural history and trying to define what's the right patient population and what's the right outcome for that particular population, and can you see it in a given amount of time that you're going to do the experiment, that you have high confidence in, and then define the patient population, is the inclusion-exclusion criteria that gets you the patient population that you have some confidence in will be declining. So that's the philosophy of what we're taking, and Matt and his team have been doing a lot of thinking about that. So I'll pass if there's anything else Matt you want to talk about.
<unk> been doing and the team has been doing the line of thinking about that.
All I'm, saying is if there's anything else unless you're 1 of the talking about.
I just spoke of I think the point.
The us.
Assuming of course. This this concept of of the Goldilocks population, where we're sure that we have the population. That's earlier adopter of disease that you have 1 of the ability to affect the disease progression, especially of our overall approach is that the upstream of the disease.
<unk> you want.
2 of the venture early enough that you can actually affect the disease progression, but also make sure that you can still have a meaningful amount of change and an untreated right because the.
Matt: Yeah, I think the point that you raised, Alex, is to reinforce this concept of the Goldilocks population, where we're sure that we have a population that's early enough in disease that you have, one, the ability to affect the disease progression, especially if our overall approach is acting upstream of the disease pathology. You want to make sure that you're early enough that you can actually affect the disease progression, but also make sure that you can The key here is to be able to show benefit over placebo, and to do that, that's really a matter of math, but during the duration of the trial, you have a placebo group that, in the absence of therapy, is going to decline enough that you can show a clinical benefit, and so we've been spending a lot of time availing ourselves of existing databases, like the EnrollHD database, with over 20,000 patients.
The key here is that when the show benefit over placebo tend to do that that's really a matter of math of during the duration of the trial placebo group debt.
Absence of therapies.
He is going to the client.
That you can show of clinical benefit and so we've been spending a lot of time of availing ourselves of.
The existing databases like the Inc.
Enrol HD database of over 20000 patients from birth I didn't have the teams and external kols as well working with us on looking very carefully.
The important factors like age CAGR of European and the number of different end points that are collected to really fine 1 debt.
That population, that's kind of move the goldilocks population as you've said and second the appropriate endpoints actually measure those changes all the time, so what youre going to see from us as.
As this work continues in our phase II trial is first and foremost obviously the goal of the phase II trials to be able to demonstrate the effect of Huntington mrna and protein lowering in huntington's disease patients will obviously be enrolling patients that based on our work.
Matt: We've got that in-house; we have teams and external KOLs as well working with us. I'm looking very carefully at the important factors like age, CAG repeat, and a number of different endpoints that are collected to really find, one, the population that's going to move, the Goldilocks population, as you said, and second, the appropriate endpoints to actually measure those changes over time.
We believe are reasonable the show that in total.
So I've changed the other measures. These importantly things like the geographic changes what we want to look at it as biomarkers of disease, both what basically the graphics to be able to then tie into.
Demonstrating the benefit of reduction in the EQT mrna and protein. So obviously to do that we want to make sure we get the night and the.
The breadth standpoint, and again have the right patients who are going.
That will change over time, so that we can show a benefit of tenants in those patients.
Matt: So, what you're going to see from us as this work goes on and continues in our phase two trial is, first and foremost, obviously, the goal of the phase two trial is to be able to demonstrate the effect of Huntington mRNA and protein lowering in Huntington disease patients. We'll obviously be enrolling patients that, based on our work, we believe are reasonable to show that in, but who will also have changes in other measures of disease, importantly, things like radiographic changes, because what we want to look at are biomarkers of disease, both blood-based and radiographic, to be able to then tie into demonstrating the benefit of reduction in HTM RNA and protein.
But on the almost going on.
Maybe I'll, let go through it I think there's some interesting.
Going on and based on the.
The experience for the <unk>.
1 was the experience of being theory.
Do plan too.
Going to discuss with them.
For accelerated approval for Q3 non op.
Relevant biomarker I mean, if you think about.
The plaque.
The book.
You know some of that with you.
Here you have.
I think even a better case.
Florida, the monitoring of the disease.
You're targeting.
On the.
The the precise.
Matt: So, obviously, to do that, we want to make sure we look at radiographic endpoints and, again, have the right patients who are going to change over time so that we can show a benefit in those cases. But on the other hand, maybe I'll also add a bit. I think there are some interesting things going on, and based on the experience with the Alzheimer's disease experience with the FDA, we do plan to discuss with them a pathway for accelerated approval focusing on a relevant biomarker.
The.
Protein, that's the mrna and thats involved in the process.
No that is due to the army's the natural.
Natural history data that shows that reduced.
The level of the renewed protein.
Extend the time before you see the onset of the disease. So the.
There is certainly is the possibility of being able to.
Alicia you don't have a discussion with the FDA.
Probably the largest talked about them as well.
The.
Group net.
A discussion of both the EMA and the.
FCA so.
Matt: I mean, if you think about the plaque in, the precise protein, or mRNA, that's involved in the process, you know that it's due to the mutant hominid. There's natural history data that shows that reduced levels of the mutant protein extend the time before you see the onset of the disease. So there certainly is a possibility of being able to at least, you know, have a discussion with the FDA, and you've probably heard LeBardus talk about it as well, that they've had discussions with both the EMA and the FDA.
That's the case, where on a very good position to.
See if we.
The good work with the endpoints from a potential accelerated approval and then with what we've been talking about could certainly the gone forever.
The.
The second study.
Great. Thanks, so much for the the color.
For taking the question.
Thank you.
Our next question comes from the line of Gena Wang with Barclays. Your line is open.
Sure.
This is the shut.
Thanks for taking our questions I have a couple of 5 on an H score of Huntington.
I think in the past the you mentioned the beyond the 15 of 30.
Matt: FDA. So, you know, if that's the case, we're in a very good position to see if we can work with that endpoint for a potentially accelerated approval. And then what we've been talking about could certainly be done for the second study. Great. Thanks so much for the color.
Mats doses do you have another 2 to 3 doses could you comment on in the <unk> data updates on how many of those sort of also.
It would include if you can share what doses.
And my second question is.
Unknown Attendee: Our next question comes from the line of Gina Wang with Barclays. Your line is open.
From the healthy volunteer trial to the phase III trial, how would you define how would you define the optimal therapeutic window.
Sheldon: Hi, this is Sheldon from GINA. Thanks for taking our question. I have a couple of 518s for Huntington.
Sheldon: I think in the past you mentioned that beyond the 15 and 30 mg max doses, you have another two to three doses. Could you comment on, in the 3Q data updates, how many dose levels would be included and, if you can share what doses there are? And my second question is, from the healthy volunteer trial to the phase two trial, how would you define the optimal therapeutic window? Thanks.
Yeah.
Sure.
So we're.
We've talked about in the past growth in the single ascending dose we went up to 135 milligram.
And the results got down to around 50% of of the RNA level, which in a way of probably 90 to 135 of equates to a 100% reduction of of the HPT and the multiple ascending dose of <unk>.
<unk> 15, and 30 milligram.
Stuart Peltz: Sure, so what we've talked about in the past was in the single ascending dose, we went up to 135 milligrams, and the results got down to around 50% of the RNA level, which, in a way, probably equates to 100% reduction of the HTT. In the multiple ascending dose of 15 and 30 milligrams, We were even at the 15 milligram dose, and we were able to get to somewhere between 40 and 50 percent reduction after 14 days of treatment.
We were even at the 15 milligram dose we are able to get sort of somewhere between 40 and 50% reduction after 14 days of treatment. So we were we were.
You could see the chose you really quite nicely.
The 50 milligram and which.
The lowest dose.
That was in our trial all of it got to that 30 milligrams. It's got the.
$216.70 per cent reduction.
No.
Clearly the you know, we're able to be able to titrate to the level of H D D.
The mrna.
Depending.
Exposure of that.
The other thing is I think what we're doing is.
Stuart Peltz: So we were, so you can see really quite nicely that 15 milligrams, which is the lowest dose that was in our trial got to that, and 30 milligrams got to about between 60 and 70% reduction, so clearly, we're able to titrate the level of HTP mRNA depending on the exposure of that. The other things I think we're doing is, as we said, looking at food effect going, food effect looking at CSF in order to We are in a good position, and the next steps will be to reproduce, and begin to look at the biomarker as a consequence of looking at the biomarker of HTT in the HD patient, just to make sure that the exposure and reduction that we see is working well.
Really as we said looking at crude affect our growth.
The fact looking at the C.
In order to share.
Tom.
In the sense in the sense we've already.
Remember in the range of where we are thinking about the dose that we want with it was somewhere between 50.15 of 30 milligrams because that gives us already the 50 per cent reduction that will probably start with in terms of reduce it. So I think we're in a pretty good position.
Position of the next steps there will be really 2.
Reproduce.
And begin to look at the biomarker as a consequence.
<unk>.
I look at the biomarker of H D. H T T in the in the H D patient just to make sure that the exposure and reduction that we see.
<unk> is doing well and then also what we said is the we're looking at the S F.
Stuart Peltz: And also, what we said is that we're looking at CSF, and the CSF is so that, and that's just a PK study, so we know that would just define and ensure that what we see in the blood is equivalent to what we've seen in the CSF. So I think, you know, what we're trying to do is obviously achieve the low, desired lowering at the lowest dose that makes us comfortable that we're in the therapeutic range where efficacy is. And we already know that with the 15%, 15 milligram dose.
And the CSF is sort of that and that's just the PK study. So we know that would get just define them ensure that where we've seen the blood is equivalent to what we've seen.
In the CSF.
So I think you know what we're trying to do is always achieved the lower the the.
Desired lowering at the lowest dose somebody sort of comfort, but we're in the therapeutics that we're in the therapeutic range where advocacy in the real.
Already know that with the 15% 15 milligram dose range.
To help you.
Sheldon: For the CSF cohorts, would that cover only one dose level, or would it cover multiple dose levels in that cohort? Unknown Speaker, It's what we're only doing
Oh, yes.
As for the CSF cohorts will that cover only 1 dose level or the covered multiple of those level in that cohort.
It's we're only doing 1 dose level of right Matt.
Matt: We're only doing one dose level, right, man? Yeah, we really only need one dose. This is simple pharmacology. We basically need the single dose level, obviously, based on the dose proportionality throughout not only the SAD and MAD work done to date but all the preclinical pharmacology modeling. I think one thing you can say that one thing that translates very well in neurodegenerative diseases is the pharmacology models from pre-clinical to clinical, right? So that what we've learned about the biological distribution and what we've learned about predictive pharmacology, we're able to test a single dose level and verify that a single dose level is
Yeah, we really only need 1 day.
This is Matt.
The simple pharmacology, we basically need the single dose level.
Obviously based on the dose proportionality of you've seen throughout the not only the sandy.
That may be worked out of the does the data put all of the preclinical pharmacology volume.
I think 1 thing you can say that 1 thing that translates very well on neurodegenerative diseases of the pharmacology models.
Items from free preclinical to clinical I sort of the.
What we've learned about the the bio distribution on what we've learned about the predictive pharmacology, we were able to assess the single dose level of their funds.
Single dose on the Lady healing.
Raj: Our next question comes from the line of Raju Prasad with Gwen Blair. Your line is open.
Very helpful. Thanks.
Yes.
Thank you.
Our next question comes from the line of Rajiv Prasad with William Blair. Your line is open.
Uh huh.
Hi, there this is on sandy on for Ike Congrats on the quarter and thanks for taking our question.
Unknown Executive: Hi there, this is Sami on behalf of Raj. Congratulations on the quarter, and thanks for taking our question. There was recently a paper published in Nature Communications that came out of an academic center in which they used an AADC gene therapy that was administered to the substantia nigra and ventral tegmental area and that ultimately led to some pretty compelling improvements in motor function. Just kind of wanted to get your guys' thoughts on targeting these midbrain regions as opposed to the detainment and if you would consider conducting a post-approval study examining the administration of PTC AADC to them. Then I have a follow-up.
It was recently of paper published in nature of communications that came out of an ask.
Academic center, and which they used in a DC gene therapy that was administered to the substantial Niagara and ventral tegmental area.
And that ultimately led to some pretty compelling and prevent the motor function just kind of wanted to get your guys thoughts on targeting the mid brain regions as opposed to the putamen and if you would consider.
Conducting a post approval study examining the administration of PTC ADC Chew them, and then I've a follow up.
Hum.
Thanks to the close to sort of.
Unknown Executive: Yeah. Yeah, thanks for the question.
That was done in the critical it on.
Unknown Executive: So that was done in the clinical setting at a university setting where they use sedative-substantive nigra. And so, you know, I think if you look at the results that we've had, where we are, it's underway in terms of what we've shown, but you know, going into the victim, the really profound results that we saw in a much larger number of patients that were looked at for five years in a clinical setting, as well as five years afterward.
Of the University setting, where the you said the suspension.
And so.
I think if you look at the results that we have.
We were on.
Of the way in terms of of what we've shown book.
Going into the retainer.
Really profound on.
The results that we saw in the much larger number of patients there was growth of about <unk>.
The debt.
5 years of clinical studies as well as.
5 years. After so we have up to 10 years of continued.
Unknown Executive: So we have up to 10 years of continued results. And I think you can, I think what we can see is that there, you know, we saw durable neurological and neuromuscular improvement again for 10 years. And I think we are the only therapy for ADC that has an active regulatory process with the EMA, which we submitted in 2020, and we also plan to submit the BLA by the end of the year.
Results and I think you can see.
See what we can say is that the debt.
We saw durable neurological on the neuro muscular improvement again on for 10 years.
Look I think we are the only therapy for ADC, That's an act.
Active regulatory process with.
The <unk> that we submitted in 2020.
And we also plan to submit the BLA by the end of the year. So I think.
Yes.
No.
Unknown Executive: So I think that we're, you know, uniquely positioned to make sure that PTC-ADC is available to all ADC patients around the world that need this, I think, transformative therapy. And I think, you know, when we thought of the reason we like to retain them is that, obviously, all patients showed improvement. And we have many patients to show that. And then the other thing that I think is an issue is that the midbrain is a much deeper structure that we think is less safe. [inaudible] to, to get to. So I mean, this lecture will be [inaudible]. All of these are requirements to bring gene therapy to patients.
We're uniquely positioned to procure the PTC.
Some of the ADC is available.
Through all of the ADC education.
Around the world.
The need this I think transformative.
Therapy and I think.
When we thought of the reason we like the butane of is that obviously is the exit all patients showed improvement.
PTC, we have many places the so then the other thing that I think of.
On the issue is that the mid range.
The much deeper structure.
But we think theres less sales.
Uh huh.
2.2.
To get to so I mean.
It's likely to be true.
On the choices that was based on the number of factors and I think the results are better but at least zone that it's really I think quite.
Cases transformative.
It's where the scope of silver dopamine neurons are.
And as.
Quite active on the big data, so we feel pretty good where we're at and then we're doing all of the other necessary regulatory of mines.
The requirements to bring the gene therapy to patients.
Unknown Executive: Gotcha, thank you, and uh separate thought, I felt like we hadn't heard too much about your oncology pipeline before, and it's a little divergent from your other therapies, which mainly target rare genetic disorders. Could you remind us what those candidates are and your clinical development strategy for them?
Got you thank you and.
Just the.
Separate thought.
I felt like we haven't heard too much about your oncology pipeline before the little divergent from here.
Other therapies, which mainly target rare genetic disorders could you so could you remind us on.
What those are.
The candidates are and your clinical development strategy for them.
Sure.
Yeah. Thanks for the next question.
Unknown Executive: Thank you for that question. The oncology program that we're working on is for two compounds. One is called Nespilin, which is, was previously 596. And then Invodastat, which is a PTC 299.
So what we're what are the.
The oncology program that we're working on is the.
It's 4.
As for 2 compounds, 1 is called the <unk> balloon, which is the <unk>.
Previously $5.96, and then.
The voters.
As of PTC, 299, and you've heard of a little bit about the with the COVID-19, but it does include of trials for a M on AML.
Unknown Executive: And you heard a little bit about that with COVID-19, but some clinical trials for AML. We are planning a deep dive update on the programs actually quite shortly and sharing the results of these programs as well. PGC on Unesco is in clinical trials for DIPG, a rare pediatric brain tumor. It's estimated to have about 300 patients per year that are diagnosed with it in the US. LMS is a rare adult solid tumor in muscles with an estimated 4,000 patients diagnosed per year in the United States.
M L.
We are planning of the deep dive update on the program actually quite shortly and sharing the results of these programs as well.
As you see.
That's the line isn't clinical trials for the I T. G. L M S.
The G is the rare pediatric brain tumor.
It's estimated to have about 300 patients.
For a year that are diagnosed in it.
In the U S.
Uh huh.
On my math says of rare adult solid tumor and muscles with an estimated 4000 patients die.
For the year in the United States. Both of these programs have high unmet medical need with really few beneficial to no treatment options.
Unknown Executive: Both of these programs have high medical needs with really few beneficial to no treatment options. And so these programs have been ongoing. So it's very much a reminiscence of a rare disorder, a rare disease approach.
So of these programs have been.
Ongoing so it's very much reminiscence of a rare disorder of rare disease.
Approach.
We anticipate having the results of the AR in the second half of 'twenty 'twenty 1.
Unknown Executive: We anticipate having the results of the clinical trials in the second half of 2021, and so I think we're quite excited about that. And with positive results here, we have the potential to initiate registration-directed trials following these results. And so we're, and then with Embodistat, it's in AML, and we also expect results by the end of 2021. So these are two additional programs, programs, and molecules that we have not talked much about what we're going to be starting. They're now getting into a position to talk to you, talk about them, and have some data that I think would be quite exciting.
For the clinical trials.
And so I think we're quite excited about that.
The west.
On the positive results here.
The potential.
We see a registration directed trial.
In these results.
And so we're and then with the voters stat, it's in AML and we also expect.
By the end of 2021. So these are 2 additional programs.
Programs of molecules that we have not talked much about what we're going to be starting the now getting into the position.
To talk to them talk about that and have some data.
The quite exciting.
Unknown Executive: Great, thank you. I look forward to seeing that data. Yeah, me too.
Great. Thank you I look forward to seeing the data.
Me too.
Thank.
The part.
I'm showing no further questions in the queue.
Operator: I am showing no further questions in the queue. I would now like to turn the call back over to management for closing remarks.
I'd now like to turn the call back over to management for closing remarks.
Oh.
Stuart Peltz: So thanks for joining us today. As we shared our second quarter highlights, I believe the progress that we've made in this quarter is really a result of the dedication of our people. And while the pandemic is ongoing, I'm really continually impressed by the development team that has made substantial progress across the full pipeline, and we're excited to continue to share these updates with you as they become available. Also, in addition to that, I think the present perseverance and execution of the global commercial team has resulted in PTC raising our 2021 revenue guidance for the DMV franchise.
Oh, thank you.
So thanks.
Thanks for joining us today as we shared on our second quarter highlights I believe the.
The progress that we've made in this quarter. It was really a result of the dedication of our people.
And while the pandemic is ongoing I I really am.
Continually impressed by the development team that has made substantial progress of course, the full pipeline.
And we're excited to continue the sphere the.
Updates.
Thank you.
Become available.
So the in addition to that that I think the president of.
Perseverance and execution of the global commercial team because of it.
Results of them.
The PTC raising our 2021 revenue guidance for the DMD franchise.
And we look forward to the.
Continue with the continued execution of this in the second half of this year. So thanks for joining the <unk>.
Stuart Peltz: And we look forward to continuing to do this in the second half of this year. So thanks for joining us and I look forward to talking to you all soon. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. [inaudible]
Look forward to talking to you all soon.
Yeah.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now go on. Thank you. Thank you.
With you.
[music].
Operator: Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent.