A lot of it's our confidence in suffice with some confidence that we may get to sell some more life out of the Duchenne franchise. In terms of the discontinuation numbers, we define that as going basically 60 days or two months with that prescription renewal.

Thank you. Our next question comes from Brian Chang with J.P. Your line is open.

Hey, guys. Congrats on a quarter.

Maybe just first, heading into the discussion with the agency on RotaPlan later this year, is the discussion going to enable you to talk about the ability to file for an accelerated approval based on the 24-month data? Is that one of the primary goals here?

And then secondly, we're seeing new patients accelerated this specific quarter, and the revenue is not catching up as fast. So, I'm curious if you can help us, you know, how do we best reconcile these two numbers? Brian, in terms of Vodafone, as you know, we had said after we shared the data that we and our team and the Navarro's team had discussed, you know, whether we would review those data with FDA. Clearly, the FDA's seeming agreement to accept a filing for the gene therapy on COHDRS's intermediate clinical endpoint was an important data point in our consideration of whether to talk to the FDA. So, you know, I think the belief is that it's important to go and talk to them, talk to them about the data. And, you know, obviously one of the important topics is going to be, you know, if there is a precedent for applications based on ICE in HD, you know, we believe our data compare quite favorably when you consider just the number of patients exposed, the dose-dependent effect seen in the stage 2 patients, the fact that we have objective data of target engagement and mechanism of action with the dose-dependent durable lowering of blood Huntington protein, as well as safety exposure in a larger number of patients in a drug that's titratable, reversible, and we have a phase 3 study that's up and going and enrollment's underway. So, we think all of those things allow for a really good discussion with FDA. And obviously Novartis has made the comment that they're still operating under the assumption that phase three is the base case. Importantly, that study has an interim analysis, but they have also commented, as we have, that we can look for any chance we have to accelerate access to a potential disease-modifying therapy given a significant unmet need for Huntington's disease patients. In terms of patient ads, look, I think what we're seeing, again, is what we said is consistent demand and consistent ads in the U.S. and increasing contributions now globally. Obviously, patient numbers come in different. Patient numbers and revenue may be different in terms of that. Patient weights may be different. There's a lot of variables that actually go into the amount of reimbursement, and obviously all patients don't enter in a quarter at one time. Some can come in a lot early, some can come in a bit later. So I think there's a lot of variables that go into it. I think, importantly, to your point, we see consistent demand. We see growth in patient numbers that, like we saw your early note, is more than folks expected. We expect that to continue, and we expect the revenue also to continue to grow over time, as we said, given the large number of patients. And, again, what we've consistently said is a significant $2 billion plus multibillion dollar opportunity. Thank you, Matt.

Thank you. Our next question comes from Judah Frommer with MS. Your line is open.

Yeah. Congrats on the quarter, and thanks for taking the question.

Are you able to add any guidance or detail on switching dynamics?

Patients that are switching from standard-of-care therapy to suffiance, Are there particular sales efforts that are generating success there? Is it word of mouth amongst patients? Anything anecdotal or tangible that would be helpful. And then just on the peak sales opportunity for Suffiance, any change in speed to peak as you're now through several quarters of the launch, or do you expect things to kind of be in line with the original expectations as of now?

Thanks for the questions, Judah.

Let me take the second one first, and then I'll ask Eric to comment a little bit on what we're seeing in the switching dynamics and some of the data that's driving that and some of the dynamics of those patients. Look, I think we've talked just generally about this being, you know, call it $2 billion plus, multi-billion dollar, not in terms of specific guidance, but just to help people understand what we believe is the magnitude of this opportunity, recalling that when we started the launch, we were getting ready for the launch, a lot of people were benchmarking this to previous therapies. I mean, I think we are now at a full year run rate that exceeds what many people thought the initial opportunity was for this product. So we've thought it's really important to really say that there's no precedent, there's no benchmarking this in terms of previous PKU therapies, but rather to benchmark in terms of what a differentiated rare disease therapy with a population of, you know, 17,000 in the U.S. and 58,000 in markets where we could access patients and get reimbursed for drug could bring. I think as we get closer, as we get further into this year and into next year, you know, we'll be in a better position to talk more about formal guidance. But again, we just have that number and have stuck that number now just to hold out the fact that one, it's a much larger opportunity than many have initially imagined. Two, what we're seeing thus far at the launch does nothing but increase our confidence that this is the magnitude of this opportunity. Eric, do you want to talk a little bit about the switching dynamics, some of the data, and what that's looking like?

Yeah, Judith, thanks for the question again. I think the first thing is that we said is we're really impressed after 12 months in the launch that we We were able to see a lot of the dynamics of those patients who are actually failed or poorly controlled, and we also saw that adults and naïve have been coming in. What we thought may have been the case was that patients and physicians who are the highest that they need would be the first ones treated. Now we have all centers of excellence who are prescribing, and we're also seeing now a significant movement to change what patients are seeing in terms of fee reduction. And I think we have a number of key programs that our sales teams, our medical teams are communicating about not just fee reduction, but how lower fee reduction is more important. And what we'll be showing at SSIEM will be some very important data that talks about normalization, patients at 120 micrometers per milliliter. And when you think about normalization, that's incredibly important because we know patients who already respond to BH4 will have a much better response to suffiance and are likely to not only reach goal, but to reach normalization. And that's going to be a very, very important part of our communication and messaging as we go forward. And that's going to be supported by data as soon as next month at SSIM. end. So we have tailored programs from a medical perspective, and we're working with these centers. And as we thought, you know, these patients who were the, you know, the most severe were the first ones to come on to therapy, but now we're seeing more and more benefits from patients who are switching, and that dynamic will continue over time.

Thank you. Our next question comes from Joseph Tome with TD Cowan. Your line is open.

Hi there. Good afternoon, and thank you for taking my questions. Maybe the first one, I guess, in that upside scenario that the FDA is amenable to a filing for Huntington's, can you talk a little bit about where you are from a CMC perspective with Vodaplam and your readiness there? And then second, maybe on the DHO-DH inhibitor program, I know it's been a while, but you also had PTC-299. Can you talk a little bit about the differences between that older agent and your next-gen compound? Thank you. Yeah, absolutely, Joe. So on the HD, look, I think this is the benefits of, one, it's a small molecule, and two, having a partner like Novartis who's well-equipped to move all of these things forward as quickly as needed. I think when we did a partnership back in 24 and then went through the official handover in early 25, you know, it's very clear that their teams are all over every aspect of getting things exactly in order for FDA approval. So, if we were given the opportunity based on the clinical data, I think we'd be very confident that that application could get there. And, of course, obviously, the confirmatory study is already up and running. In terms of the HODH inhibitor, yeah, I think PTC299 was really a legacy product, and as one would expect from a, when you go from Gen 1.0 to, I would say, wait, this is, I guess, technically 2.0, but it's more like a 3.0 or 4.0 in terms of how much more potent and specific it really is. And, you know, I think we had a lot of conversations internally about bringing this molecule forward, but when we saw how differentiated it is in understanding that there have been other DHO-DH inhibitors that have been approved that have been viable commercial products, And to be able to benchmark PCA4-4 to those, and we showed those data at our research day, as well as 299 and showed the superiority in terms of in vitro potency as well as specificity for the DH and DH target, tells us that we're now able to target a mechanism known to be important and do so in a very selective, specific, and potent way. So we look forward to the Phase 2A study. We're going to be doing that in a population of patients with significant inflammation with rheumatoid arthritis, that's not our intended indication, but rather what we want to do is take a population in whom we knew would have a biomarker profile of inflammation that would allow us to establish the relationship between DHO levels and effects on biomarkers of T-cell and B-cell immunity that can then help us inform where we would go from there in terms of specific target population. Great.

Thank you. Our next question comes from Faisal Kershid with Jeffries. Your line is open.

Hey, guys. Thank you for taking the question. I'm just going to ask a couple of nitty-gritty commercial things, if you don't mind. Could you comment if there were any inventory effects for Cefiants in the second quarter? And then can you also comment on how we should be thinking about and modeling things like gross to net and like net pricing and average patient weight, have your assumptions that are changed at all?

Yeah, I would thank you for the questions. I would simply say, we've had no inventory effects to think about. Things have been fairly constant in that regard, I would say, as well, in terms of patient weight, patient age, gross net, all those things have been consistent. We haven't seen any real changes there. Thank you.

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

Hi, everyone. This is Nevedon for Brian. Thank you so much for taking in our questions. Just one more on the science, how are you kind of thinking about the split of revenues over the long term, especially just given that the ex-U.S. is progressing so well and you seem to be getting pretty good reimbursement and pricing there, and just given that there is kind of a larger population outside the U.S. as well? And then I'm also wondering if you could talk about your updated thoughts on BD and And if your kind of appetite has changed there, if you're looking at any specific programs or therapeutic areas, and what's the size of any potential deals that you might be able to do with? First, on the split, look, I think it may be a little early to give an exact breakout. I think we think that international can be a significant contributor here. Still, the vast majority will likely always be driven by the U.S., but I think there could be a significant contribution ex-US when you start looking at that number of patients and what we believe we're going to be able to achieve in terms of in terms of reimbursement but it's all early for us to give an exact exact breakdown there um you know i'd say for example what we're seeing thus far in in japan uh has been really impressive you know there's maybe a thousand one hundred patients there at pku but we're seeing a lot like the u.s so there's early demand. There's patients not on therapy who are coming back in and getting on therapy. There's centers of excellence. And as Eric mentioned, the prepared comments, you know, there we have a price on par with the U.S. Price is set for 10 years. It's very easy for patients to get on drugs. So, you know, again, there's a lot of these kinds of stories out there where we've seen international markets be able to start to make an impact that we expect will continue to grow in the latter part of 26 into 27 and beyond.

Pierre, do you want to talk a little bit about how we've been thinking about bd yes happy to so first of all i would say we closed the quarter with very strong cash position of 2.2 billion dollars we work really hard to get there um and as we said we our team has demonstrated their ability to launch products globally that's a key strength of ours they have uh capacity so we're looking at bd in a number of ways uh one obviously we're still laser focus on safe finance we don't distract the momentum at all are there ways to complement that very strong franchise for us that's one bucket we're also looking at you know other areas in a rare disease space late stage or commercial again to leverage that global infrastructure that we have so that's how we're thinking about it again we want to make sure we are very disciplined in any potential transaction to make sure that we create value for shareholders you mentioned size, again, we're not going to do anything where we would lever up and use, you know, all our cash in one go. So that's how we think about it. Thank you so much.

Thank you. Our next question comes from Luke Herman with Baird. Your line is open.

Thanks for the question, team. So now that you're established in all the centers of excellence for suffiance, has there been any shift in the proportion of new starts stemming from sort of a proactive visit as compared to a more typical checkup schedule? And sorry if you've already covered this, but to the extent you're able to qualify, how have new starts tracked into July? Thanks.

Thanks for the questions, Luke. I would say that we, what we've been hearing from a lot of the KOLs is that most of the prescriptions are coming now as part of regular visits. So, You know, early on, we said in the first couple months of launch, there were a lot of folks coming in, waiting lists, and a lot of attention in the first part, but most of the KOLs and prescribers have told us that somewhere late November or so, we saw a shift, and it's really as patients are coming in, they're looking to start them on therapy or switch them, for Now, that being said, we still note that, you know, one of the questions earlier asked about what the effects of us going to conferences and the team, the work that our customer-facing teams do in the field and our patient support and patient engagement work does. We know that the more messages, the more patients hear about this, there still is a lot of patient pull and market pull to get into clinics and get on the drug. In terms of starts into July, what we've said is that overall, you know, we continue to see strong underlying demand. We expect it to be consistent growth in the U.S., accelerating growth outside of the U.S., and a lot of that is what underpinned or prompted our confidence and our ability to raise guys in state 50 to 950.

Thank you. Our next question comes from Joe Schwartz with Lyric Partners. Your line is open.

Thanks very much. I guess I have a question on Germany first. I think the pricing and reimbursement for suffiance was previously expected to be finalized this summer with other European negotiations advancing behind that. Why is it seeming to take longer? Are you getting the traction you expected? And will it hold up any of the discussions with other European countries in any way?

Thanks, Eric. Eric, do you want to talk a little about the negotiations globally and particularly Germany?

Yeah, and in fact, keep in mind, thanks for the question, keep in mind that we've launched in Germany and it has been just barely on the 12-month cycle. We have a number of what we call mandatory negotiation sessions, and then there are informal ones with GKV. Clearly, those discussions have been productive. They've been cordial. We've been working on that. We've just now hit the summer months. So those discussions will continue throughout the summer. It's likely that our pricing and reimbursement will be finalized sometime in the third quarter, but it could go into the fourth quarter. The list price right now that we have listed in the lower tax is very similar to the U.S. price. It has not affected any of the other markets. And in fact, Brazil, which CMED has referenced in terms of innovation status, the current Brazilian price is linked to the German price. So essentially, everything is going according to schedule, and we anticipate to have the final decisions sometime in the second half of this year.

Thank you.

Thank you. Our next question comes from Paul Choi with Goldman Sachs. your line is open.

Hi. Congratulations on the progress, and thanks for taking the questions. I have two on Huntington's. Matt, I was wondering if you could maybe offer your preliminary thoughts on development of PTC-303 as a monotherapy in Huntington's versus potential combination use with Vodoplam. Any early thoughts there would be great. And my second one is Roche recently discontinued its tominersen studies in Huntington's and, you know, caveating for the usual cross-trial and cross-drug differences. Any thoughts there just on the, you know, implications just given, you know, what was early, you know, and promising biomarker changes versus what looks like, you know, less success on clinical endpoints and just, you know, any thoughts on potential read-throughs there?

Thank you very much.

Yeah, absolutely. So, first, look, we're super excited about PTC 303. We talked about it at R&D Day. And I think, again, this shows PTC's ability to leverage splicing to bring forward potentially valuable and impactful therapies. And PTC 303 is one that can target several diseases characterized by somatic expansion. This is one that I think from conception to getting to a development candidate took our team probably a little less than three years, which is phenomenal, and really, I think, is an example of how we're getting smarter and using the tools we have to facilitate and accelerate small molecule splicing development. As you pointed out, Paul, and we talked about it on the call, HD is a disease of somatic expansion. Targeting MSH3 is probably now the hottest target in Huntington's disease drug development. We're very excited about Vodoplam. We think they could work together, and also it could serve as a monotherapy, particularly in, for example, juvenile HD, which in a juvenile HD is a setting where there's a large number of triplet repeats and it's characterized by rapid progression. What does that mean? There's rapid somatic expansion. So you would think that something targeting somatic expansion, you could see a signal sooner and maybe louder in a short amount of time in, say, a juvenile HD population. But, you know, we're very excited to be able to have this as a potential therapeutic option. We We look forward to getting all of the IMD-natal studies done and getting this into the clinic as quickly as we can in 2027. In terms of trauma-nursin, I think it's been quite clear for a bit of time now, probably ever since the Generation HD1 data were presented, and probably even before that, when some of the earlier stage data were presented, that a lot of the challenges of trauma-nursin were not really a mandate or a reflection of the potential of HCT lowering, but a lot of it was associated with the limitations of the ASL modality here. As was noted in earlier studies of Tominursin, particularly when there was a four-week dosing arm, it had to be discontinued because of the significant amount of inflammation created in the CSF by the ASL. And in fact, in the doses used in Generation HD1 as well as Generation HD2, you still saw white blood cells and protein, markers of immunoinflammatory response in the CSF of patients who received it. That's been noted. That's something that has always been a concern. If you think about it, you're taking eight Huntington's disease patients, and a lot of those patients were later stage patients. So these are individuals who had brain inflammation and oxidative stress for decades, and you are dropping an inflammatory stimulus into their CSF. And so what ends up happening is you can't actually, I think, readily or easily detect a favorable Huntington-lowering response because it's confounded by a significant inflammatory response in that population. And again, that's corroborated by the protein and white blood cells in the CSF as well as by some of the other issues with the CSF that were observed in that study. And of course, the association at certain points of NFL spikes following treatment, And all of that put together is really why I think a lot of people view the Toma-Nursin experience as really a reflection of that drug and not HG2-lowering. You know, we think that the RISD paradigm is probably a better way to think about Vodoplan, Oral small molecule splicing agent gets full brain biodistribution, allow for titratability, allow to use the peripheral blood cells as a marker for target engagement and change of protein of interest and then really allow you then to identify a therapeutic window so that you can deliver benefit along with safety. So that's how we think about it.

Great. Thank you.

Thank you. I'm showing no further questions. I'd like to turn the call over to Dr. Matthew Klein for closing remarks.

Thank you again for joining the call this afternoon. We are incredibly excited about our performance so far in 2026. and we look forward to continued outstanding performance not only with Defiance but across the entire company. Thank you all again for joining the call.

Thank you for your participation. You may now disconnect. Everyone enjoy the rest of your day.