PTC Therapeutics Inc (PTCT) 2017 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the PTC Therapeutics second quarter financial results conference call. (Operator Instructions) As a reminder, this conference is being recorded.

I would like to introduce your host for today's conference, Ms. Emily Hill. Ma'am, please begin.

Good afternoon, and thank you for joining us to discuss our 2017 second quarter corporate updates and financial results.

Before I hand the call over to our CEO, Stuart Peltz, 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 facts, including statements concerning financial guidance; our expectation with respect to future commercial availability of and access to EMFLAZA, the anticipated benefits of the EMFLAZA acquisition; our future expectations regarding other clinical, regulatory and commercialization matters, including with respect to potential outcomes and anticipated time lines; anticipated milestones and time lines of our SMA collaboration with Roche; 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 continued commercial launch of EMFLAZA, including our ability to secure adequate pricing, coverage and reimbursement terms of third-party payers for other products in a timely manner, whether and to what extent third-party payers impose additional requirements before approving EMFLAZA prescription reimbursement; our ability to integrate EMFLAZA into our business and realize the anticipated benefits of the acquisition; changes in laws and regulations; our ability to resolve the matters set forth in the Refuse to File letter we received from the FDA in connection with our NDA for Translarna for the treatment nmDMD, including whether our filing of the NDA over protest with the FDA will result in a timely or successful review of the NDA; and those risks discussed under heading, Special Note, regarding forward-looking statements and risk factors in our second quarter Form 10-Q, 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 on today's earnings release.

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

Thanks, Emily, and thanks for joining us this afternoon. We are thrilled to report on the success of our business across multiple areas. This quarter, there has been significant advancements spanning our commercial, clinical, regulatory and research programs. In particular, we will review the commercial progress we have made with our 2 products, EMFLAZA and Translarna as well as the regulatory process for our Translarna application in the United States. I will also share advancements we've made in our spinal muscular atrophy program, including meaningful data recently presented at 2017 CureSMA meeting.

Let me start with a commercial update. In mid-May, we launched EMFLAZA in the United States for all Duchenne muscular dystrophy patients aged 5 years and older. As we said before, we acquired EMFLAZA in part because we understood from the placebo arm of our Duchenne clinical trials and the results from other industry and natural history studies the strong clinical benefits EMFLAZA provides for Duchenne patients.

We launched EMFLAZA with the intention of making this crucial therapy available for all eligible United States Duchenne patients. We are following through on this commitment and are happy to report that only 12 weeks into the launch, there are already over 1,200 patients on EMFLAZA. Our goal is to ensure broad access to all eligible patients. To that end, we have worked hard to minimize out-of-pocket cost for patients. To date, the monthly out-of-pocket burden for eligible patients has been close to 0.

Duchenne treatment guidelines recommend corticosteroids as a foundational component of the standard of care. EMFLAZA is the only corticosteroid approved for Duchenne muscular dystrophy in the United States. We believe EMFLAZA should be prescribed to all eligible patients, and we are working towards this goal of broad access. We continue to see a positive response from patients and providers. We have also seen support from the payers, resulting in positive reimbursement decisions. We are pleased the conversion of bridge to commercial had been faster than we originally expected.

Though still early in the launch, based on the progress to date, we are raising our 2017 EMFLAZA guidance from $15 million to $20 million. We will continue working diligently to make sure EMFLAZA's clinical benefits that we observed in our clinical trial and other trials is understood by patients and providers.

Our investments in finding treatments for Duchenne muscular dystrophy started almost 20 years ago, focusing on RNA biology to treat disease-specific mutations. These research and development efforts resulted in what is now Translarna. Translarna enhances the ribosomal read-through of a nonsense mutation to allow the production of full-length dystrophy. Translarna is currently commercially available in over 25 countries worldwide.

In the 3 years since launch, we have seen tremendous uptake in the European Union and Latin America. And most recently, we have begun expanding into the Middle East and Central and Eastern Europe. Patients and physicians have expressed benefits from the therapy, and compliance to date remains over 90%. We are pleased to report the strongest quarter for Translarna since launch 3 years ago with revenue of approximately $46 million. At this point, we are increasing Translarna's 2017 guidance to $120 million to $140 million.

We are working diligently to bring this important therapy to nonsense mutation Duchenne muscular dystrophy patients in the United States. Translarna has a PDUFA date of October 24, and the FDA has tentatively scheduled our Advisory Committee Meeting for September 28. We are eager for the opportunity to present the evidence supporting Translarna's benefits. We also look forward to hearing the perspective of key stakeholders, including Duchenne patients and their families. Some of whom have had access to this therapy since our first trial over 10 years ago.

We are actively preparing for a potential United States launch. Our commercialization of EMFLAZA allowed us to establish an infrastructure in the United States, which we can leverage to quickly launch Translarna.

Let me now switch gears and touch on our SMA program, a joint development collaboration with Roche and the SMA Foundation. Let me remind you, we have an SMN2 oral splicing modifier, RG7916. This quarter, we reported important clinical results from an interim analysis of the data from the SUNFISH study in Type 2 and 3 SMA patients. We anticipate that this study will transition to a pivotal phase in the coming months.

An additional trial, FIREFISH, is evaluating RG7916 in Type 1 SMA patients. This study is also expected to transition to the pivotal stage later this year. As an oral small molecule with broad tissue distribution, RG7916 has the potential for important clinical benefits and commercial differentiation. We will share more with you on the results later in the call.

Our pipeline also continues to progress with additional indications for Translarna and programs in our splicing and oncology platform. Lastly, we are proud to be in a strong financial position. As you will see, the revenue generated from our commercial assets, Translarna and EMFLAZA, greatly offsets our cash burn and moves us towards operating as a sustainable business. We will walk through these programs starting with a detailed commercial review from Mark Rothera. Mark?

Thanks, Stu. I'll focus first on Translarna, our therapy approved by the European Medicines Agency for nonsense mutation Duchenne muscular dystrophy. Translarna is available in over 25 countries worldwide, including Europe, Latin America, and more recently, we have been expanding the Middle East and Central and Eastern European regions. In these countries, Translarna is obtained through either commercial access or reimbursed early access programs. As Stu mentioned, this was our strongest quarter for Translarna sales since launch. We generated net revenues of approximately $46 million, which represent nearly 200% growth versus the same quarter last year. Sales from Latin America contributed to the strong growth this quarter. As we said before, some of this contribution includes large orders from Latin America that can come at irregular intervals. Overall, we have seen good growth in all regions we operate in.

As stated before, growth in Translarna comes from both increasing penetration in existing territories as well as the addition of new geographies in Central and Eastern Europe and the Middle East. We are working through final pricing and reimbursement negotiations in select countries. Notably, Translarna has been evaluated by Germany's benefit assessment bureau twice and both times, received a positive rating.

As we've discussed multiple times, we have been successful with an alternative importation pathway, which has allowed commercial access for both new and existing patients. As a matter of process, we will engage in another round of price arbitration. We will have the choice to remain on the importation path regardless of the outcome. We expect the arbitration process to be completed this quarter.

In France, we have completed the Health Technology Assessment review and received a rating of ASMR V. We are moving to pricing and reimbursement discussions with the French authorities and expect these negotiations to conclude no earlier than by the end of this year. Based on the overall dynamics of the business, we are in a position to raise Translarna's 2017 guidance as Stu mentioned earlier.

Now I'll shift to the launch of EMFLAZA, which is for all eligible United States Duchenne muscular dystrophy patients 5 years or older irrespective of their mutation. The launch of EMFLAZA, which started in mid-May, has been a great success. This is in part because of our 20-year commitment and heritage to DMD as well as the deep commercial experience of our team. Working with patient groups, physicians and payers to ensure broad access to EMFLAZA continues to be our priority. I am happy to report that more than 1,200 patients in the U.S. are now receiving EMFLAZA through commercial or bridging programs just 12 weeks post launch.

We have presented placebo data from the ACT DMD trial at the ISPOR International Meeting in May, which shows that patients on EMFLAZA had a benefit in muscle function, which correlated with up to 4 years in delayed loss of ambulation. This data was part of the motivation for the EMFLAZA acquisition, and we are proud to bring this therapy to all eligible U.S. patients, most of whom previously did not have access.

Specifically on access, coverage has been strong. To date, 47 states are covering EMFLAZA in Medicaid programs, and over 170 private insurers have authorized EMFLAZA reimbursement. Collectively, over 250 million lives are covered by these private and public insurance programs. Importantly, the average monthly out-of-pocket cost for EMFLAZA to patients is close to 0. We'll continue to provide patient numbers for the remainder of this year as a useful metric to track the launch. Beyond 2017, we will solely provide revenue guidance.

As Stu mentioned earlier, we are increasing our 2017 revenue guidance for EMFLAZA to $15 million to $20 million from $5 million to $10 million. This is a reflection of the early success of the launch and our execution in bringing access to patients broadly. We continue to convert prescriptions and see solid growth ahead.

As we progress with the launch, the next phase will include the challenge of educating physicians and patients to broaden the use of EMFLAZA to those who are naive to corticosteroid therapy. Based on the efficacy and safety profile, we believe EMFLAZA should be standard of care for all eligible patients.

The most important aspects of the message we want to share with key stakeholders is the efficacy benefit seen with EMFLAZA. As mentioned earlier, the data from our ACT DMD trial shows that patients on EMFLAZA had a benefit in muscle function, which correlated with up to 4 years in delay to loss of ambulation. Additional datasets will be published this year and are important for key stakeholders to appreciate the magnitude of the benefit from this therapy.

I'm very proud of what we've built here at PTC over the last 4 years. We are now a global commercial organization with a highly talented team in the orphan space, representing 2 of the 3 approved DMD-specific therapies in the world.

And now I'd like to turn it back to Stu.

Thanks, Mark. Before we move on from the commercial updates, I wanted to take a moment and thank Mark for his hard work and effort over the past 4.5 years. Mark is moving on in his career, and I want to recognize the tremendous achievement of building our global commercial enterprise and successfully positioning us as a sustainable commercial business.

Over 20 years, PTC has evolved from a small New Jersey R&D-focused biotech to a global commercial stage company with continued R&D innovation. As you are aware, we recently restructured and are now positioned to maximize our commercial clinical and research assets going forward.

Let me now provide a few additional updates on the development program for Translarna. We have 2 ongoing studies for Duchenne muscular dystrophy. The first is a pediatric PK and safety study of Translarna in children ages 2 to 5 years old, which will be completed this year. Our intention is to file for an extended label in this population. Our long-term study in Translarna opened to start enrolling patients this quarter. As a reminder, this trial is a specific obligation of our EMA approval.

We are also excited about the ongoing Phase II Translarna studies in both aniridia, Dravet and CDKL5, and we'll be highlighting these Phase II clinical trials at our upcoming Analyst Day later this year.

Let me now switch to another one of our programs, 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 earlier in life and is the leading genetic cause of death in infants and toddlers.

We have a robust program collaboration with Roche and the SMA Foundation around oral SMN2 splicing modifiers. Spinal muscular atrophy is caused by reduced levels of SMN protein due to deletion or mutation in the SMN1 gene. The oral compound, RG7916, we have in clinical development is designed to drive alternative splicing of the pre-mRNA to produce increased levels of full-length mRNA and functional SMN protein. We believe that an oral therapy with exposure throughout the body, which includes both peripheral tissues such as muscle, liver, bones and nerve tissues, will be more beneficial than those focused on just the central nervous system.

The lead compound, RG7916, is currently being studied in 3 clinical trials in SMA patients. SUNFISH is a double-blinded placebo-controlled randomized study. The first part has enrolled approximately 50 SMA Type 2 and 3 patients. The second pivotal phase of the study is planned to enroll 168 patients with a 12-month endpoint of motor function measure. Interim data analysis from the dose finding phase of SUNFISH was recently presented at the CureSMA meeting.

The interim data demonstrated an approximately 400% increase in the SMN2 full length the Delta7 mRNA ratio in a dose-dependent manner. A linear relationship was observed between median exposure levels and increase in the ratio of full length to Delta7 SMN2 messenger RNA. For reference, RG7800, our first compound, demonstrated an approximate average increase of 100% in SMN2 mRNA, which translated to an average 50% full-length SMN protein. The interim analysis also noted that while the first cohort of patients had been on therapy for 6 months, no toxicities requiring patient's withdrawal had been observed in the clinic. Additional data from Part I of SUNFISH, including protein level, will be presented at a major medical meeting later this year. The SUNFISH study is expected to transition to a pivotal phase in the coming months.

FIREFISH is an open-label 2-part study in SMA Type 1 infants. The current ongoing dose escalation phase of the study is enrolling up to 10 patients. The study will then transition to 40-patient pivotal trial. The primary endpoint is sitting without support as assessed in the Bayley gross motor scale. The enrollment of FIREFISH patients is focused on geographical areas where other therapies are not yet available. FIREFISH is also expected to transition to a pivotal portion later this year.

The SMA program also has an open-label trial known as JEWELFISH. JEWELFISH allows SMA patients from other studies of SMN2 splicing targeting therapies, including our previous candidate, RG7800, to roll over to RG7916. This trial was developed out of request from patients and their families for continued access to our oral splicing therapy.

The collaborative work ongoing with Roche and the SMA Foundation demonstrates the selectivity of our splicing technology. Outside of this collaboration, we are also pursuing additional preclinical programs, targeting pre-mRNA splicing. Exciting work in both Huntington's and Familial Dysautonomia is ongoing. At an Analyst Day later this year, we will share more about these splicing programs as well as highlighting our R&D pipeline for next-generation read-through program, our oncology program and our clinical development program for Translarna in other indications.

I'd like to now to turn the call over to Christine Utter, our Principal Financial Officer. Christine?

Thanks, Stu. I am pleased with the strong performance this quarter. We reported our first EMFLAZA revenues and achieved our highest quarterly Translarna revenues to date. Translarna revenue in the quarter was $45.8 million, a 73% increase over the prior quarter. As Mark noted earlier, certain large orders from Latin America contributed to this notably high quarter of Translarna revenue. EMFLAZA revenue was reported at $2.1 million. The early launch of EMFLAZA has been a successful process. The performance of both of these commercial products allows us to increase our 2017 revenue guidance, which I will detail shortly.

I now like to review our financial details for the second quarter of 2017. We reported a net loss of approximately $17.5 million for the second quarter of 2017, which declined over $21.4 million from a $38.9 million loss for the same period of 2016. Our operating losses are anticipated to continue declining as we leverage our existing infrastructure and continue to grow our revenue base now with 2 commercial products.

GAAP R&D expenses were approximately $30.8 million for the second quarter of 2017 compared to approximately $28.8 million for the same period in 2016. Non-GAAP R&D expenses in the second quarter were approximately $26.9 million compared to $24.6 million for the same period in 2016, representing a year-over-year increase of $2.3 million. R&D expenses have increased as a result of the initiation of long-term DMD study and increased regulatory costs, partially offset by expenses associated with the completion of our CF program.

GAAP SG&A expenses were approximately $28.9 million for the second quarter of 2017 compared to approximately $23.4 million for the same period in 2016. Non-GAAP SG&A expenses were approximately $24.9 million for the second quarter of 2017 compared to approximately $18.3 million for the same period in 2016, an increase of $6.6 million. SG&A expenses have increased mostly driven by the launch of EMFLAZA.

We would like to take the time today to review our 2017 revenue and operating expense guidance. We are updating our Translarna net revenue guidance to $120 million to $140 million, up from $115 million to $130 million. As we noted, Translarna revenue remains strong with growth continuing in both new and existing territories. This guidance assumes the current exchange rate and a continued commercial expansion for Translarna and nonsense mutation DMD outside of the U.S.

We are also raising EMFLAZA guidance to $15 million to $20 million, up from $5 million to $10 million to reflect the early success of the launch. We also anticipate a $20 million milestone payment related to the SMA program in the second half of the year for a potential total 2017 revenues of $155 million to $180 million.

We are reiterating our GAAP operating expense guidance for the year 2017 between $250 million to $260 million. Excluding estimated noncash stock-based compensation expense of approximately $40 million, full year 2017 non-GAAP operating expenses are anticipated to be between $210 million and $220 million. These expenses are expected to be primarily in support of the continued research and clinical development of our product pipeline candidates as well as a commercialization of Translarna outside of the U.S. and investing in the commercial launch of EMFLAZA in the U.S.

Our previous cash guidance was to complete 2017 with approximately $100 million. Due to decreased cash burn, we now anticipate ending the year with over $120 million of cash and marketable securities. We're happy to end this quarter in an even stronger financial position.

Let me hand the call back to Stuart.

Thanks, Christine. It's been a great quarter. Before we hand over the call for Q&A, I wanted to let everyone know, considering the FDA's ongoing review of our Translarna NDA and upcoming AdCom and PDUFA, we will not be making further comments beyond our prepared remarks on this regulatory process.

Okay, operator, can you open the line for Q&A?

(Operator Instructions) Our first question is from Alethia Young of Crédit Suisse.

This is Derek on for Alethia. I have like one question. So beyond the 1,200 patients you have, I'm wondering how many patients like actually [use] (inaudible) but still waiting, and how many percentage of patients got denied by the payer. And any kind of like pushbacks on the payer on the pricing side will be helpful.

Yes. Thanks, Derek. Thanks for the question. As we said, we -- yes, things have been moving well. We currently have 1,200 patients either on insurance or on bridging. I should make the point they -- all those patients are -- have insurance, and so we anticipate they'll all ultimately turn into commercial payers. And while we don't give precise numbers and -- or don't give numbers or disclose on the prescriptions, I think the fact that we've increased our guidance from $5 million to $10 million to $15 million to $20 million, I think, is a reflection of that. And I think -- and this is, in a sense, a consequence really of just how fast the conversions have -- going. So we feel good about it, and we think that there's still a pipeline of patients to go through the process.

Our next question is from Matthew Eckler of RBC Capital.

So I wondered if you can comment a little bit about the average age and average weights of the 1,200 patients currently on EMFLAZA as well as what trends you've seen so far and then how you think that could change going forward.

Yes, sure. Thanks, Matt, for the question. So just to remind everyone, we previously disclosed that we anticipate that for 25 -- that a typical patient is about 25 kilograms, and the net price would be $35,000. And that's really what we're disclosing. At this point, we're not disclosing about additional average weights. What we did is the 25-kilogram typical patient is what we ultimately expect in terms of the prescribing patterns for DMD. So at this point, it's actually probably still too early in the launch to see where ultimately that would go.

And then could you talk a little bit about what you're seeing in terms of the prior authorization requirements for EMFLAZA?

Yes, sure. So in terms of prior authorization or step added what we expect -- first of all, I should say that reimbursement coverage is obviously going pretty well in that it's reflected in the increasing in guidance that we did. We anticipate or have seen predominantly either prior authorization or step added previously, and so -- but we've been able to either get through that relatively rapidly so that -- while they're there, we haven't seen that yet to be a major problem thus far. So these patients who have been on -- many of them who have been on deflazacort are actually getting rapidly through the conversion process.

And then just one more quick one here. You mentioned there'll be additional EMFLAZA data later this year. Could you provide any more detail on what that data is and when we might see it?

Yes. So as you may recall, we had a poster of our results -- of the top line results from our trial -- from the trial from the placebo group, which looked at the patients that who were on placebo but who are on prednisone versus deflazacort and will be -- and then in that -- and that poster described the benefits that we saw of deflazacort over EMFLAZA -- I think they're the benefits of EMFLAZA over prednisone. And so -- and I think what you'll see is there'll be additional work. I know there's a publication that will be coming out from the CINRG Natural History Study looking at the natural history and the positive effects of corticosteroids in general but also then calling out the comparisons of EMFLAZA versus prednisone. And again, you'll see the benefits of EMFLAZA over prednisone within that publication as well. And then there'll be some discussions, I think, and work at some point in some of the Lilly data, which also has a placebo arm, which also has prednisone and EMFLAZA. And you'll see the consistency of the results of where EMFLAZA patients did better than prednisone patients there as well. And I think we'll have something where we will use not only our data but also combine the data in a meta-analysis. So I think, at the end of the day, what you're going to see is a fair number -- a fair amount of evidence that is just showing the benefits of EMFLAZA and why we think it should be ultimately the standard of care for these patients.

Our next question is from Paul Choi of Barclays.

I guess, my first question is on SMA, and you mentioned that you would have SUNFISH data later this year. But can you -- any -- with regard to the transition to a potential pivotal trial here, can you comment on how you're thinking about the primary biomarker endpoint versus your potential secondary functional endpoints? And will this transition to the pivotal trial include any sort of meaningful motor milestones as well as endpoints?

Yes. Thanks for that. So just to -- again, just to remind everybody, we had seen -- we had -- we, Roche and the SMA Foundation, there was a nice poster showing that a 400% increase in the amount of SMN full-length transcript versus the SMN2 Delta RNA. And so that was a significant increase. And just for comparisons, if you look to what we had in RG7800 before, we had 100% increase in the -- of the full-length transcript and about a 50% increase of protein level. That was the average amount. So you're seeing a substantial increase with RG7916. This is what we reported at the SMA meeting, was RNA level. Later this year, we'll be talking about the protein levels, and that will be at a meeting hopefully this year as well. And then what we will do is transition from -- it was a escalating dose phase, then transitions into a pivotal phase. And the purpose there is, obviously, to go -- to have the biomarker, which we're continuing to measure. And again, we're able to because it's a systematic -- the drug itself is a systematic drug, and it has exposure to all tissues. And that's why we can look in the blood and therefore see increased levels both in RNA and protein. So that's the advantage of that. And then when we transition, for instance, in the FIREFISH -- I mean, or in the SUNFISH study, that's a 12-month study that uses a motor function, the MFM scale, to measure at 12 months of treatment, and therefore, we'll look at the -- within that, the various measurements within that trial and also then be able to calibrate that to the levels of SMN protein. The FIREFISH is -- and that was Type 2 and 3 patients. In the Type 1 patients, we have -- that's for Type 1 patients, and there, we're using the Bayley infant scale, which basically looks also at sitting unassisted at 12 months. So those are the clinical benefit outputs that we'll be looking at.

And then just as a follow-up to the potential trial design there, how are you thinking about age stratification potentially within the Type 2 and Type 3 populations? Is there any sort of sense that there would be any better response with earlier or younger patients and how we should potentially think about them -- that as a factor in your trial design and potential outcomes?

Yes. So basically, I think we're doing some stratification of -- in the Type 2, 3 patients of 2 to 11 and 12 to 25 in terms of the stratification that are there. And those information, I think, you could see at the ClinicalTrials.gov for details of the trial design.

Our next question is from Anupam Rama of JPMorgan.

It's Eric in for Anupam this evening. Just a couple ones on EMFLAZA from us. Just wondering if you could talk a little bit about the concentration of the physician prescriber base here to start and how we should be thinking about sort of the pace of patient adds looking out beyond this initial bolus. And then I know you -- Stu, you're kind of hesitant to comment on sort of average patient weight and age at this point, but I'm just wondering, if -- with regard to kind of net pricing going forward, whether there is any anticipated activity as it relates to sort of discounting given your experience thus far in the commercial setting.

Yes. So that's a good question. In terms of the physician's use, I think it's been widely used around the country. I don't think there's any net in one area versus the other. I think there's use around the country. I think the way we think in general about this is obviously there is pent-up demand early, and we said prior to the launch, we had a bolus of about 900 scripts that were ready to actually get through the process. And so that has been ongoing. And so there's obviously a fair amount of progress that we've made into that. We are finding also on top of having EMFLAZA patients, there are also some naive patients. But you can imagine that ramp or that bolus that we've had recently of those that have been on EMFLAZA and that are rapidly transitioning into EMFLAZA -- commercial EMFLAZA. And so that's been going a while. We think there's -- we do see some of the naive patients also getting through. But I think the next phase of what we'll be doing is to get patients who haven't been on any corticosteroid before, that is to get through this process. And we imagine that could take more time than what we've seen here. So we still think there's growth that will occur that then could transition to a change of that slope as it takes time to get patients on from naive to on EMFLAZA. And that's -- and aspect also of talking to physicians, explaining the data that we have and others are putting on so that they'll be -- that they understand that we think, ultimately, our goal is to make EMFLAZA the standard of care for these patients. Did I hit everything? Was there another...

The second follow-up is on net pricing and just sort of sensitivity to the initial pricing assumption or net pricing assumption given your level of sort of discounting or kind of buying down of co-pays that you currently experienced.

Yes, sure. So obviously, what we've said is we're looking at $35,000 for 25 kilos, what we're -- what we've disclosed. Our goal, obviously, is to broad access for all patients, and we're working towards that. As I said in my prepared remarks that, really, the co-pay and other, we have very strong programs, and therefore, our goal was to make sure that patients wasn't out of pocket expense and we've seen, thus far, well, really low to de minimis levels of out of pocket expense. So that's actually gone well. So that's where we are right now in terms of our understanding of the co-pay. That's been going well. The program's been doing well. And what we're disclosing is the 25-kilogram patient, $35,000.

Your next question is from Alexandria Huynh of Cowen.

Just I'll start with one on Translarna. Can you give us any more detail on the relative contributions of revenues from Latin America? And are there any particular quarters you would expect to be bulk orders?

To be what? Oh, bulk orders, yes. Thanks, Alexandria, for that question. So obviously, we've disclosed overall revenue. We think, in general, it's actually going quite well, which is why we raised the guidance to $120 million to $140 million. There are -- Latin America has been growing quite well and what we -- but there is within -- not only with Brazil and other countries. There are irregular orders that go on, and so that will be bulky. There will times like -- there'll be lumpiness in terms of orders. So it is growing well. But I should point out, really, that all regions -- and that's in count and part why we raised revenue. All regions are still actually growing in revenues.

And then just one on EMFLAZA. You've previously mentioned doing a study for potential label extension into younger patients. Can you give any more details on your plans for those and when we could expect the trial?

Yes, sure. Currently, the label is 5 and above. There is a plan to go into patients under 5, 2 to 5 -- 2 to 4 -- get to 2 to 4 years olds, and we're working through that now on what -- on moving forward that in terms of how best to do that. So that's in the plans now and working up the protocol.

Our next question is from the Joel Beatty of Citigroup.

This is [Shawn] calling in for Joel. I appreciate you taking time for my questions. Regarding the 7916 compound, what duration of follow-up and what data would be most important to give you confidence in the decision to advance the program?

Yes. Thanks, [Shawn], for that question. So we're -- actually, already the results that we're talking about -- we're showing you is a 400% increase in terms of the RNA levels, and we'll have the protein levels that we'll report to all of you some time this year. But that gives us -- we already -- that going to give us great confidence. What we're really doing in the 2-part study is that in the first part of the study it's really to do an escalating dose phase to find the highest dose that gives us the change in the splicing. From that, it's a seamless transition into the pivotal trial phase, where we go on and do the clinical benefit. So really, the decision, it's not a go, no go decision. It's a decision on which dose do we go to.

Great. That's very helpful. And as a quick follow-up, are you able to give any enrollment updates on the SMA Type 1 and the JEWELFISH study?

Yes. I think what we're saying is that the first parts of both studies will be completed this year, so in the coming months, that will then transition into the pivotal studies.

Thank you. At this time, there are no other questions in queue. I'll turn it to Mr. Peltz for closing remarks.

Well, thank you. I think, as you can see from this quarter, we're at an infection point where we have had 2 commercial products -- where we have 2 commercial products and an innovative R&D engine. Our mission has always been to provide treatments to patients living with rare diseases, who have limited treatment options. I'm proud Translarna, the first therapy for nonsense mutation Duchenne muscular dystrophy patients, and we remain dedicated to working with physicians, patients and their families to bring Translarna to the patients in the United States. We're also pleased with the successful early launch of EMFLAZA. Consistent with the mission, we're working to ensure broad access to all eligible EMFLAZA Duchenne muscular dystrophy patients. Thank you all for joining the call.

Ladies and gentlemen, thank you for your participation in today's conference. This concludes your program. You may now disconnect. Everyone, have a great day.