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Edited Transcript of PTCT earnings conference call or presentation 9-May-18 8:30pm GMT

Q1 2018 PTC Therapeutics Inc Earnings Call

South Plainfield Jun 7, 2018 (Thomson StreetEvents) -- Edited Transcript of PTC Therapeutics Inc earnings conference call or presentation Wednesday, May 9, 2018 at 8:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Christine Utter

PTC Therapeutics, Inc. - Principal Financial Officer & Treasurer

* Emily Hill

PTC Therapeutics, Inc. - Executive Director of IR

* Marcio Souza

PTC Therapeutics, Inc. - COO

* Stuart W. Peltz

PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director

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Conference Call Participants

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* Brian Corey Abrahams

RBC Capital Markets, LLC, Research Division - Senior Analyst

* Gena Wang

Barclays Bank PLC, Research Division - Research Analyst

* Joel Lawrence Beatty

Citigroup Inc, Research Division - VP and Analyst

* Raju Yashaswi Prasad

William Blair & Company L.L.C., Research Division - Senior Research Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and thank you for your patience. You've joined the PTC Therapeutics 2018 First Quarter and Corporate Updates and Financial Results Conference Call. (Operator Instructions) As a reminder, this conference may be recorded.

I would now like to turn the call over to your host, Head of Investor Relations, Ms. Emily Hill. Ma'am, you may begin.

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Emily Hill, PTC Therapeutics, Inc. - Executive Director of IR [2]

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Thank you. Hello. Good afternoon. And thank you for joining us to discuss our 2018 first quarter corporate updates and financial results. Joining me on today's call is our CEO, Stuart Peltz, our Chief Operating Officer, Marcio Souza, and our Principal Financial Officer, Christine Utter.

Before I hand the call over to Stuart, I would like to remind you that today we will be making forward-looking statements. These statements include all statements other than those of historical fact, including statements concerning financial guidance, our expectations with respect to the future commercial availability of and access to Emflaza and Translarna, the timing and outcome of any future resubmission of an NDA for Translarna to the FDA, our future expectations regarding other clinical regulatory and commercialization matters, including with respect to potential outcomes and anticipated timelines, anticipated timelines of our SMA collaboration with Roche and the SMA Foundation, addressable patient populations for Translarna and Emflaza, and the potential success of Translarna for the treatment of nmDMD and Emflaza for the treatment of DMD.

Actual results may differ materially from expressed or implied by forward-looking statements as a result of a variety of risks and uncertainties, including those related to our commercialization of Emflaza and Translarna, including our ability to secure adequate pricing, coverage, and reimbursement terms with third-party payers for our products in a timely manner, whether and to what extent third-party payers impose additional requirements for approving Emflaza prescription reimbursement, changes in laws and regulations, our ability to resolve the matters set forth in the denial of our appeals to the complete response letter we received from the FDA in connection with our NDA for Translarna for the treatment of nmDMD and those risks discussed under the headings forward-looking statements in our form 10-Q for the quarter ended March 31, 2018, and risk factors in our form 10-Q for the quarter ended March 31, 2018, and in our form 10-K for the year ended 2017, which is available from the SEC and on our website.

Such statements represent our judgment as of today, and PTC undertakes no obligation to publicly update any forward-looking statements except as required by law. We will disclose certain non-GAAP information during this call, information regarding our use of GAAP and non-GAAP financial measures, and a reconciliation of GAAP to non-GAAP is available in today's earnings release.

With that, let me pass the call over to Stu.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [3]

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Thanks, Emily, and thanks for joining us this afternoon. Joining me on the call today are our Chief Operating Officer, Marcio Souza, and our Principal Financial Officer, Christine Utter. Marcio will provide the commercial and internal clinical development updates. Christine will end the call with a thorough review of our first quarter results and our strong financial outlook.

We've had a busy first quarter in 2018. As we recently highlighted at our 20th anniversary Analyst Day, we have several developing programs across the Duchenne franchise, splicing platform and niche oncology pipeline. Our DMD franchise is growing with Translarna available in many countries outside the United States for nonsense mutation Duchenne muscular dystrophy and with Emflaza here in the U.S. for all DMD patients over 5.

Over the past 2 decades we have worked to bring therapies to patients with rare disorders beginning with Duchenne. We are now expanding on that experience to bring differentiated therapies to patients with high unmet medical need. Our vision is to continue to build a fully integrated rare disease biotech company that leverages our deep science expertise and world-class commercial capabilities. We are now in the position of having 2 commercial products and we have built an effective global commercial operation. We seek to leverage our commercial platform by continuing to deliver new and differentiated therapies in rare disorders.

Our commercial success with both Translarna and Emflaza is a reflection of our understanding of the unmet needs for Duchenne patients. We work diligently to ensure patients have access to therapies that make a difference to them. Our commercial execution has led to strong year-over-year revenue growth. In the first quarter of 2018, our revenue for the Duchenne franchise totaled $56 million. Our guidance for full-year 2018 is between $260 million and $295 million. We have also set a 5-year goal for the compounded growth of Translarna revenue of 15%.

Beyond the current growth opportunity for Translarna outside the United States, we are also looking to expand and bring Translarna to U.S. patients. To that end, we are working to design and initiate a dystrophin study for potential U.S. approval of Translarna. The FDA has informed us that dystrophin data combined with clinical results in our NDA would be sufficient for an application towards accelerated approval. We expect to initiate such a study by the end of the year.

Let me now turn to our internal science research programs and our pipeline. I'll start with our internally developed splicing platform. We have an oral small molecule as a treatment for SMA, or spinal muscular atrophy, advancing in the clinic. This program is currently in pivotal studies in partnership with Roche and the SMA Foundation. The ongoing pivotal studies include FIREFISH for Type 1 SMA infants, and SUNFISH for Type 2 and 3 SMA patients. Encouraging interim data from the dose-finding portions of both studies were recently presented at the annual meeting of the American Academy of Neurology in April. I'll provide more details on that later in the call.

In addition to SMA, our splicing platform has generated Huntington's disease and familial dysautonomia programs. These are progressing and are currently in the lead optimization stages. We expect both programs to advance into the clinic by 2020.

Our niche oncology program is also advancing. We are focused on rare oncology indications where we can leverage our RNA biology expertise in addressing high unmet medical need. There are currently two advanced candidates, PTC596, which is currently in the clinic, and PTC299, which we anticipate will reenter the clinic later this year. I'll discuss these programs in more detail later in the call.

Let me now pass the ball over to Marcio, who will update you on our clinical and commercial efforts. Marcio?

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Marcio Souza, PTC Therapeutics, Inc. - COO [4]

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Hey, thanks, Stu. 2018 is off to a strong start for our DMD franchise, with 2 out of the 3 approved DMD therapies worldwide. Emflaza is approved in the U.S. for all DMD patients 5 years and older, and we are pleased with the progress to date and look forward to further expansion of Emflaza use.

Translarna is available outside of the U.S. for nonsense mutation DMD patients. As you know, the label for both therapies currently cover patients 5 years and older, and it's a well understood concept that treating earlier patients with DMD would allow for muscle preservation and therefore better patient outcome. Aligned with our focus on superior care for patients, we're investing heavily in programs to lower the average age of diagnose worldwide. Currently, patients in most countries have an average delay of diagnose after presentation of symptoms of more than 4 years. We're investing genotyping and disease state awareness campaigns to improve this standard of care for DMD patients globally.

Complementary to that effort, we're also working to expand the labels of both Emflaza and Translarna to patients aged as young as the age of 2. Our application for a label expansion for Translarna is under review with the European regulatory authorities, and we expect a CHMP decision by midyear. We are also working to finalize a pediatric study for Emflaza in the United States.

Now we'll focus on our commercial performance and expectations, beginning with Emflaza. We launched Emflaza in the U.S. in the middle of May last year. The initial strategic rationale for Emflaza acquisition remains the same, as we are marching forward to establish Emflaza as the standard of care for DMD patients in the U.S. We are pleased by The Lancet publication in November of last year of the Synergy 10 years natural history study, showing a clear benefit of Emflaza. This was further reinforced by the updated DMD standard of care guidelines, recommending Emflaza initiation at the time of diagnose.

We have completed our first initiative of transitioning deflazacort experienced patients to commercial therapy, and we are now expanding Emflaza use to the segment of patients who have previously used or are currently on prednisone. We have a number of initiatives under way to ensure that Emflaza is established as the standard of care in these patients.

Additional publications are expected which will reinforce the benefit of Emflaza over prednisone. Emflaza education programs and conference presentations also allow us to share the data supporting the benefits for DMD patients of Emflaza. Because of this data, we understand the need to bring Emflaza to all DMD patients as early as possible. We are proud that through an optimized [specialty] pharmacy distribution and the high-touch patient support programs, we have achieved broad access with low out-of-pocket cost for patients.

Reaching naive patients is another critical step in our long-term strategy. It is known that in the U.S., about 50% of the DMD patients are still not currently treated with any corticosteroid therapy. We believe this is a result of the historical view of the risk benefit of a less safe and less effective drug that predates the Emflaza data publications and our launch efforts. This is now reflected in the current DMD treatment guidelines. We have a long-term strategy to penetrate the segments of untreated DMD patients, as well as to expand the label to address the youngest patients, aged 2 to 5.

Now switching gears to Translarna. As Stu said, we remain committed to bringing Translarna to the U.S. patients, and at the same time we continue to expand the adoption globally. We are pleased the FDA has recommended a path forward towards accelerated approval, and our intention is to quantify dystrophin in Translarna-treated patients in 2 parallel cohorts, one cohort in patients who have been treated with Translarna for at least one year, and another one in naive patients.

We are currently focused on validating the methods for dystrophin quantification, and we intend to initiate this study by the end of the year with expected readouts during 2019. Outside of the U.S., we first launched Translarna in 2014. We are confirming our expectation for a 15% composite growth through end year 2022. We're excited about Translarna's growth outlook. The main driver for future growth will continue to be new patient initiation on Translarna globally.

During Q1 we saw growth in patients uptake in all geographies. It's not uncommon in ultra orphan disorders to continue to identify patients once the treatment is available, and we continue to have success in patient identification in all geographies we operate. Patients and physicians have expressed the benefit of treatment from Translarna, and compliance, as previously reported, has remained very high, over 90%.

I'd like to point out, as we have before, that there is a significant [variability] in the ordering patterns in certain Latin America countries, and why we do not guide revenues on a quarterly basis. Our annual Translarna revenue guidance of $170 million to $185 million takes into consideration expected variability of these quarterly ordering patterns and reflects the underlying patient demands. The global commercial Translarna business and Emflaza acquisition have diversified our product portfolio, revenue and geographic footprints, positioning PTC as an outstanding rare disease business development partner. We have now demonstrated the ability to integrate a product and successfully launch in a challenging therapeutic area.

As Stu mentioned earlier, one of the goals for our future growth is to be opportunistic in in-licensing and acquiring assets to build out our pipeline while [also] invest in our internal developments.

Let me now provide a short update on the developments programs. As we've described before, we appreciate the perspective of the DMD [community] on the importance of treating patients as early as possible in order to preserve muscle function. We plan to conduct pediatric study for Emflaza, as requested by the FDA. This study, upon completion, would provide us an additional 6 months of market exclusivity. We intend to initiate this study in 2018.

Additionally, we have completed a PK study of Translarna in children aged 2 to 5. Data from this study was the base of our submission for label expansion to the EMA, which is currently under review. Both of these efforts align well with the intent of the DMD guidelines to begin treatment at the time of diagnose. Our long-term Translarna study, 041, started enrolling patients in the third quarter of last year. As a reminder, the conduct of this study is a specific obligation of our EMA approval and the FDA has stated this could serve as a confirmatory study in connection with a potential accelerated approval in the U.S. We expect this study to be fully enrolled in 2018 to meet our specific obligation with EMA.

At our Analyst Day in April, I spoke about the strategy of our niche oncology pipeline and I wanted to touch more on that today. As Stu mentioned, we are focused on rare oncology indications. We have 2 lead assets, PTC299 and PTC596. 596, our candidate for solid tumor, was designed to have properties to allow blood-brain barrier penetration and avoid efflux pumps such as PGP. That contributes to tumor resistance. This program is currently focused on addressing rare solid tumors with high unmet need.

We aim to start new clinical trials in 2 solid tumor indications this year. The other development candidate we are very excited about is PTC299. 299 is a potent DHODH inhibitor, which is in development for hematological malignancies. We have prior clinical experience with 299 in solid tumors which demonstrate good dose linearity and [speedy] response. While generally well tolerated, 2 serious events of drug-induced liver injury occur, resulting in a clinical hold and the discontinuation of the program in solid tumors.

Based on the response we have seen in clinic, we perform extensive work to better understand the mechanism of action for 299 and identify patient populations with tumor types which are sensitive to DHODH for our clinical path forwards. We found PTC299 demonstrate broader and more potent activity against leukemic cells than against solid tumors, which we expected will enable us to dose at much lower levels in the clinic.

We plan to move PTC299 back into the clinic in hematological tumors in the third quarter of this year. We also have a fast follower DHODH inhibitor currently in late stage chemical optimization. We're confident that we are well equipped to drive value with both strong commercial and clinical capabilities and a continued focus on transforming lives of patients with rare disorders.

With that, I'll hand the call back to Stu. Stuart?

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [5]

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Thanks, Marcio. I'd like to share more detail on data recently generated in our SMA program. Most of you are familiar with the program, which is based on our small molecule splicing platform. This technology has been used to discover potential new therapies for spinal muscular atrophy, or SMA, a rare genetic neuromuscular disorder that generally manifests early in life and is the leading genetic cause of death in infants and toddlers.

We have a robust program in collaboration with Roche and the SMA Foundation around oral SMN2 splicing modifiers. We believe that an oral systemic therapy provides a competitive advantage because of its broad tissue distribution and the use of administration. Earlier clinical data has been shown that RG7916 drives SMN2 splicing towards a complete restoration of full-length SMN2 messenger RNA.

This program is currently in pivotal stages with 2 registrational studies, FIREFISH for Type 1 infants, and SUNFISH for Type 2 and 3 patients. The JEWELFISH study, while not registrational, is also enrolling patients from other splicing therapies. Data from JEWELFISH and from the dose-finding portion of FIREFISH and SUNFISH were presented at the annual meeting of the Academy of Neurology in April.

Data from the dose-finding portion of the FIREFISH study included SMN protein level increases of up to 6.5-fold with a median increase of 3.2-fold. Data from the 21 babies enrolled was presented at the AAN, and highlighted continual survival. Previously published natural history data indicate that the median age of event-free survival for SMA Type 1 infants to be between 8 and 10.5 months. Of the 21 babies presented, 9 have surpassed the natural history expectations of 10.5-months survival. It was also noted no babies have required a tracheostomy or permanent ventilation since study initiation, and no baby has lost the ability to swallow.

The median age of first dose was 6.7 months, and babies have received RG7916 for a duration of up to 14.8 months. As of the April presentation, RG7916 has been well tolerated at all dose levels and there have been no drug-related safety finding leading to withdrawal. It was previously reported in January that 2 babies died due to disease progression and the deaths were determined not to be drug-related. The FIREFISH dose-finding study is now complete, and all babies are being transitioned to the therapeutic dose for an extension trial.

Ongoing data presentation from this trial is expected throughout 2018, including more survival data, CHOP-INTEND scores, and other motor milestones. We look forward to sharing these developing data with you.

As you may have heard from several key opinion leaders at our Analyst Day in April, now that survival data has been presented in SMA babies, the bar has been raised. Physicians and families look forward now to treatment therapies that allow SMA patients to achieve developmental milestones and have broader function. Recruitment is ongoing globally for the pivotal part of FIREFISH study. The primary endpoint of this registrational study is the percentage of infants who are sitting without support at 12 months of treatment as assessed by the Bayley infant scale.

Presentations on the SUNFISH and JEWELFISH studies also supported safety and tolerability of RG7916. Data from the dose-finding portion of SUNFISH was also presented at AAN, showing that SMN protein levels increases of approximately 2.5-fold were sustained for up to 35 weeks. In October 2017, SUNFISH entered the pivotal stage and is currently enrolling. At that time all SUNFISH patients from dose-finding study were transitioned to the therapeutic dose and have been maintained with no dropouts or serious adverse events.

Lastly, preclinical data were also presented demonstrating that RG7916 increases SMN protein levels in several tissues, including brain, muscle, and blood. These increases were proportional and correlated. These results demonstrate the relevance of SMN protein levels, increases in blood as the predictor of SMN up-regulation in the target organs such as brain and muscle.

The SMA program is not only progressing towards an oral and systemic treatment for SMA patients. It also validates that our splicing platform technology can identify selective compounds that modulate pre-mRNA splicing. We are now applying our expertise to other challenging diseases with high unmet medical need and have internal preclinical programs. These include programs in Huntington's disease and familial dysautonomia. We expect both programs to enter the clinic by 2020. We are very excited about our splicing programs and covered them in depth at our Analyst Day, and I refer you to those slides on our website for full details.

I'd like now to turn the call over to Christine Utter, our Principal Financial Officer. Let me pass it over to Christine.

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Christine Utter, PTC Therapeutics, Inc. - Principal Financial Officer & Treasurer [6]

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Thanks, Stu. Earlier today we issued a press release summarizing the details of our financial results for the first quarter of 2018, and I refer you to that release for full details. I'll start with a few comments on our financial performance and our guidance for 2018.

Starting with our topline results, we reported strong performance across our DMD franchise. As Stu mentioned, our results for first quarter of 2018 were as expected, with reported total net product revenue of approximately $56 million. Based on where we stand today, we are reiterating our 2018 guidance of $260 million to $295 million. Translarna net product sales were $36.8 million for the first quarter of 2018, representing 39% growth over the prior period, driven by both expansion into new territories and increased penetration in existing geographies.

Emflaza net product sales reflect success of the launch, with reported revenue of $19.2 million in the first quarter of 2018, having just launched in May 2017. Total revenues for the first quarter of 2018 were approximately $56 million, compared to $26.5 million in the first quarter of 2017. The change in total revenue was a result of the growth of Translarna and the successful U.S. Emflaza launch.

Non-GAAP R&D expenses were at $27.6 million for the first quarter of 2018, excluding $3.7 million in non-cash stock-based compensation expense, compared to $22.9 million for the same period in 2017, excluding $4.5 million in non-cash stock-based compensation expense. This increase in R&D expense reflects increased investment in our research programs and the advancement of our clinical pipeline.

Non-GAAP SG&A expenses were at $29 million for the first quarter of 2018, excluding $4 million in non-cash stock-based compensation expense, compared to $20.9 million for the same period in 2017, excluding $4.6 million in non-cash stock-based compensation expense, reflecting continued investment in our commercial activities for our DMD franchise.

Net loss for the first quarter of 2018 was $19.3 million compared to a net loss of $29.1 million for the same period in 2017. This decline in net loss reflects our growing revenue base as we continue to leverage our successful international corporate infrastructure. Cash, cash equivalents, and marketable securities totaled approximately $178.3 million at March 31, 2018, compared to $191.2 million at year-end 2017.

In April we successfully completed a public offering of 4.6 million shares of common stock, raising $117.9 million in the public market. We intend to use the net proceeds from this offering primarily to transact in potential business development opportunities and to fund and accelerate our research and development efforts, including our programs for alternative splicing and our niche oncology pipeline.

I will now hand the call over to the operator and start our question-and-answer session. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Brian Abrahams of RBC Capital Markets.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [2]

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First question on Translarna commercially. Can you tell us a little bit more about whether you saw any inventory effects, seasonality, the impact of ordering patterns in the first quarter and where you are quarter-over-quarter with respect to patient demand and volume and persistence and compliance?

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Marcio Souza, PTC Therapeutics, Inc. - COO [3]

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So we did see, as you probably recall, Q4 was a very strong quarter for us last year, so we had a lot of demands for both patients and some orders that came very late on that quarter. So we had, to some extent, a carryover that is not what I would call inventory building because we really don't see like patients carrying inventory or like payers carrying inventory for a long time for Translarna, but there is some effect of that as we transition from the end of the year to this year.

The important thing that we're seeing as we look into and what gives me comfort and optimism towards the end of the year is we saw like patients being added in every region as I mentioned a few minutes ago, and the compliance is still remaining pretty high. We're not seeing drop-offs like to the later part of your question. Historically we've seen more than 90% of compliance and persistence, and we are still seeing exactly that same range in all regions. We're adding patients. There is always a little bit of delay here and there at the very beginning of the year, so I'm not sure if I was going to call that much like a seasonal effect as it is like just holidays and things like that that impact. But nothing major that we are seeing in terms of the dynamics of the patients. I hope that answer the question.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [4]

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Yeah, that's very helpful. And then on the U.S. approval-geared studies and investigations for Translarna, can you maybe help us understand a little bit better what the comparison would be for the patients who are on drug for at least a year in terms of dystrophin levels? Would that be compared to baseline levels for the naive group, or would you be using sort of historical data from other sources? Maybe help us understand how that data would all fit together, the naive versus the experienced patients.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [5]

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Yeah, we would use sort of a combined control that would be untreated patients so that would -- you know, what we're looking for obviously is to represent what a baseline would look like, which I think -- and there is some precedent for this in which how Sarepta had done this previously. So we would use that as the baseline and compare the treatment of patients who have been on for some time to that control.

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Brian Corey Abrahams, RBC Capital Markets, LLC, Research Division - Senior Analyst [6]

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Got it. And one more for me if you don't mind. With respect to the SMA program and 7916, what would you be looking for in terms of the milestone and functional data as we kind of see data evolve over the course of this year at the more therapeutic doses and with longer follow-up? Is there any specific goal, and I'm also curious with respect to whether there's any specific symptoms, like respiratory symptoms, for instance, that you might be particularly focused on to help us understand whether there's improved brainstem penetration versus available therapies?

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [7]

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You know, obviously we're pretty excited about RG7916 and we think it has the potential to be best in class because of the systemic nature of it, and I think there's a lot of data now that we've shown pre-clinically how it passes the blood-brain barrier and that the levels of protein in the blood represent in a sense about a 1-to-1 that we've seen not only in rodents but also in non-human primates as well, so we're pretty confident of that as well.

And just to remind everyone we saw up to a 6.5-fold increase in the Type 1 babies, and we talked a bit about the survival and how we're passing the milestones on that in terms of the 8.5 months and how 16 babies have surpassed the 8.5-month line. So we feel pretty good about that, and over the coming months obviously we're going to look at all the motor milestones as well, hopefully giving about CHOP-INTEND, baby sitting, all that will come -- as it comes through and it gets formally looked at as the data accrues.

So that's where we're at. That's what we hope to be able to talk about and at least describe as the year goes on.

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Operator [8]

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Our next question comes from the line of Gena Wang of Barclays.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [9]

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Thank you very much for taking my questions, and apology if some already discussed. I missed the beginning of the call. Just wanted to ask regarding I think this quarter, any inventory impact, stocking, destocking for both Translarna and Emflaza?

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Marcio Souza, PTC Therapeutics, Inc. - COO [10]

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Yeah, we've seen -- I mentioned this a little bit before, but we did see a little bit of, I wouldn't call inventory buildup, as I mentioned, in terms of patients getting shipments late in Q4, so obviously the use of that shipments go through Q1, so just that's the natural use that we see. In some geographies they end up getting -- specifically for Translarna, they start getting for like more than a month or so. So there is a little bit of the spillover throughout the year, but it's not really inventory as much in a strict sense, but the use patterns that we see throughout the year. So that impacts a little bit the very beginning.

With Emflaza specifically, there isn't much of that dynamic. What we see is really the use and the authorizations being happening pretty much throughout the month and the beginning of the month. It's harder to ship as well close to the holidays in the United States so we try to get that all done as early as possible, so not as much, even for this small amount that I described for Translarna, we don't see that happening for Emflaza.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [11]

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Okay. And any more color regarding -- I don't know if you comment earlier -- regarding the number of patient beyond the initial bridging programs, like new patients for this quarter for Emflaza?

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Marcio Souza, PTC Therapeutics, Inc. - COO [12]

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Sure. So we stopped disclosing specific patient numbers in Q3 last year, but just to give you a little bit of color on that. So we've seen growth in patients like are pretty happy with what we are seeing in terms of (inaudible) from the field, the programs we put in place. We moved to this, what we call the second phase of the launch now, so pretty much the bridging that you mentioned before and the patients who were previously experienced with deflazacort, they've been transitioned.

So what we are seeing more and more now is in the second phase, as I described, the patients who are being treated with like prednisone, prednisolone, or like any other forms that there's a lot of stuff, a lot of ways these patients are being treated. You're starting treatments, you stay on that treatment, and we are pretty happy with the trajectory that we are seeing right now, but obviously the work does not stop and we're looking every day on how to make this better and how to get more patients on what we believe ultimately is best for them. It's the only approved treatment in the U.S. and the best standard of care.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [13]

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And then just one quick question regarding SMA program. Can you just remind us like in terms of a rough timeline that you and/or Roche will present SMA functional data, and also if you can just remind us in terms of onset of the drug like how quickly, once you start to dose the patient, how quickly you will start to see the protein level increase and if that could translate into the clinical benefit.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [14]

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Yeah, thanks for that, and just as we were talking about a little bit ago, that we have the SUNFISH Type 1 study, the part 1 where we talked about previously where we had, of the 21 babies, we talked about previously 2 had passed that were non-drug-related and that 16 babies already are alive with a key milestone of 18.5 months. So just to remind everyone that the median age of enrollment was about 6.7 months and they've been on drug for up to 14.8 months.

So what we're going to be doing is going to be presenting data throughout this year, and obviously we're excited about that and stay tuned, we'll be talking about -- we'll be going from not just survival data, but going then we'll be talking about the motor function milestones and measurements like CHOP-INTEND, put out baby sitting, other things -- talk about all the important milestones that we'll be measuring throughout the year, and we intend to have such discussions during as we see them and decide that we need to present that, describe them or to have them at scientific meetings. So that's our plan. So we plan to have hopefully a significant number of discussions with you over the year.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [15]

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And then just a quick question regarding how quick onset the drug once you start to dose the patient.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [16]

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So, I mean, obviously it's an orally bioavailable systemic drug that gets into all tissues. We saw in blood that it occurs actually quite rapidly, where you start seeing production of the protein. You know, you give it for a day, you get RNA [made] and then from there you get protein relatively quickly so you can measure quite rapidly.

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Gena Wang, Barclays Bank PLC, Research Division - Research Analyst [17]

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Okay. So that happen usually in days, right? You would be able to see.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [18]

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Yes. That's correct.

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Operator [19]

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(Operator Instructions) Our next question comes from the line of Raju Prasad of William Blair.

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Raju Yashaswi Prasad, William Blair & Company L.L.C., Research Division - Senior Research Analyst [20]

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As far as the dystrophin study for the U.S., have you met with the FDA yet or do you have any kind of incremental color on the type of data that you'll have to submit and potentially from what parts of the body or what muscle types?

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Marcio Souza, PTC Therapeutics, Inc. - COO [21]

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So we've been talking to the FDA, very happy with the openness that the agents have had with us in terms of being even a little bit more informal in some of the communications and keeping the door open for back-and-forth that we might require with them. As we mentioned late last year that we would be talking to them during Q1, and we do regularly talk. What we are focusing right now really with our understanding of some of these conversations is that the key is really for us to pick the methods, continue collaborating with them, and understand like what the decision wants to do in terms of the qualification.

So we are running a few tracks in parallel based on that. We have some stuff we did in-house and some collaborations we are doing externally with private labs as well on the quantification. That's the rate limiting. As I mentioned before and we discussed at the analyst events on April 17, we expect to start this trial in the U.S. before the end of the year. We see no issues whatsoever right now and [march towards] that date, and it's really a parallel track between the clinical initiation and the methodology to be validated.

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Raju Yashaswi Prasad, William Blair & Company L.L.C., Research Division - Senior Research Analyst [22]

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And then just a quick question, in the press release for the Part 2 of the FIREFISH study, the endpoint is the proportion of patients sitting without support after 12 months of RG7916 treatment, does that assume that the patients' median age is going to be around 6 months? I thought it was kind of an 18-month endpoint for other companies.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [23]

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So, no, right. So it's the number of patients sitting after 12 months and unassisted for 5 seconds.

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Raju Yashaswi Prasad, William Blair & Company L.L.C., Research Division - Senior Research Analyst [24]

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And that's agnostic to the age they are when they're enrolled in the study, so if it's a 1 or 2-month-old, it would be when they are 13 or 14 months?

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Marcio Souza, PTC Therapeutics, Inc. - COO [25]

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That's correct. I think it's important for us to remind here, right, so if you look into Part 1, these patients were fairly old and they had to be symptomatic at 3 months, no later than 3 months, when it's a little bit different when you look into other data sets that are out there, these are like what I'd call (inaudible) are the most severe Type 1 patients we are seeing like the median age on the last card that we showed to you guys was 6.7 months. So, independently of all of that, and we discussed this before, we are very confident on how this study is going and we're looking forward to show that. So it's [irrestrictive] of, to answer your question directly, restricted to the dates they are enrolled is 12 months after enrollment.

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [26]

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And maybe just as a little color to that, part of the reason we chose that they had to be -- been diagnosed by 3 months, because it is an open label study, so that that really sort of defines them as a truly Type 1. And the outcome of that is we're looking for a 5 or greater out of 40 would be statistically significant.

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Operator [27]

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Our next question comes from the line of Joel Beatty of Citi.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP and Analyst [28]

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The first one is on the SMA program. Could you share any data to date on the differences between dose levels that you saw in part 1 of the study, and including any information you might be able to provide on how the eventual dose that was chosen for the pivotal part of the study was chosen, as well as any implications from the dose-finding study in terms of the effects you might expect to see in the first patients that were enrolled compared to the patients that were enrolled later in the study?

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [29]

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Yeah, sure. I think obviously the first part was really a dose-finding study, and really the doses, we're looking both at variables such as age and weight as part of that. And so once we completed that portion, we're now moving them up to what we think is the efficacious dose and following them from all those -- from there. So I think that's sort of the point where everyone is on equal playing field in the sense of having the same dose, is now occurring.

So they all weren't on the same dose, and we were picking the dose really based on, we had the advantage of having the PD marker that lets us look at the level of SMN protein, so you really could actually get -- define how well you're doing by that dose. So that was the key part of this.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP and Analyst [30]

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Got it. And then one other question. On the 15% growth this year from Translarna, could you give any color on, is this expected kind of across the board, or what particular regions or groups do you expect to contribute to that growth the most?

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Marcio Souza, PTC Therapeutics, Inc. - COO [31]

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Sure. So the 15% composite growth until 2022 rights that we gave as a guidance, the expectation there on the base is really driven by patient accrual. So we expect to continue to accrue patients globally. What we are seeing right now, what our projections show, what the programs put in place are supporting is that this growth is going to continue to come for all geographies that we operate. Like beginning of the year, like on the last couple months we've seen this materialize in other geographies. We're happy with the progress on patient identification, we're happy with the progress in terms of genotyping. And as we expand obviously, in the later years, the remaining patients and the more percent-wise growth is going to come for the regions that are less penetrated like the Middle East and Africa, CEE and Latin America. But in general, all the regions are growing and they're all included in the potential.

I think it's worth to mention as well, as I talked in the remarks a few minutes ago, we are in the last stage of the conversations with EMA for the label expansion for the 2 to 5, and that's going to add more patients to the pool, we're going to be able to treat them globally, and we hopefully are going to be resolving this in the next couple months with EMA and we're going to be able to launch the product later this year or beginning of next year and start to accrue patients.

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Operator [32]

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

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Stuart W. Peltz, PTC Therapeutics, Inc. - Co-Founder, CEO & Executive Director [33]

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Thank you. And thank you all for joining the call, and as you can see we're pretty excited about 2018 and we think this is going to be a really important year for us with several milestones that we think are going to potentially drive value creation. And we'll continue to grow the Duchenne franchise, we're going to present additional data from our SMA program, and we'll be sharing more on the oncology pipeline.

In addition, it's our goal to do at least one transaction in business development this year to add something else on, so I think there's a lot of value generation to occur, and I thank you for joining the call today.

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Operator [34]

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Thank you, sir. Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day.