BioCryst Pharmaceuticals, Inc.

Good morning and welcome to the BioCHRIST first quarter 2024 earnings call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing star then zero on your telephone keypad. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to John Bluth at Biochrist. Please go ahead.

Thanks, Drew. Good morning, and welcome to Biochrist's first quarter 2024 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO John Stonehouse, CFO Anthony Doyle, Chief Commercial Officer Charlie Geyer, and Chief R&D Officer Dr. Helen Thackeray. Following our remarks, we will answer your questions. Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information, as well as the company's future performance and or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. In addition, today's conference call includes non-GAAP pro forma financial measures. For reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the press releases section of our investor relations website at www.biocrist.com. I'd now like to turn the call over to John Stonehouse.

Thanks, John. We are off to a fantastic start to the year with growing Orladeo revenue and our pipeline advancing on schedule. Orladeo revenue in Q1 exceeded our expectations as the commercial team in the U.S. did a great job successfully navigating the reauthorization process faster than previous years. Charlie will share more detail, but now, in the fourth year since approval, the steady and consistent growth of new patients shows no signs of letting up, and we are even more confident we are on track to reach our goal of $1 billion in global revenue at peak. We continue to make great progress with our prioritized pipeline too. Our Orla Dale pediatric program is on schedule to file for approval next year. We continue to make progress with BCX 10013 and expect we will be able to decide on whether to partner or discontinue the program later this year. In addition, our other pipeline programs, including BCX17725 for Netherton's and Avoralstat for DME, are advancing toward the clinic with first or best-in-class profiles. Over the next 12 months, Orladeo will be approaching the midway point of our global peak revenue goals. We'll be preparing to file for approval for Orladeo use in pediatric patients and we'll be starting to move multiple pipeline programs into patient studies. And last but not least, we will be approaching profitability. The year is off to a strong start with exceptional progress in all these areas, and we are focused on continuing this momentum throughout the year. With that, I'll turn it over to Charlie to share the outstanding performance of Orlodeo for the quarter.

Thanks, John. During the quarter, we continue to execute our global plan for Oral-Ladeo very effectively. Revenue of $88.9 million exceeded our expectations because of the efficient handling of prescription reauthorizations in the United States, combined with the continued strong demand as healthcare providers gain confidence in Oral-Ladeo. Based on these improvements and trends, we are raising our 2024 Oral-Ladeo revenue guidance to the top half of our prior range, and now forecast $390 to $400 million for the year. I'll describe these improvements and trends more specifically. Last year, we invested in our patient services and market access teams with a goal of improving efficiency and effectiveness of patients to paid therapy. The first quarter shows that these investments are working. Two facts stand out in this improvement. First, our patient services team completed more benefits investigations in January, than we did in the entire first quarter of 2023, resulting in patients getting back to paid therapy quicker than in previous years. Completing these investigations early in the first quarter gives our better understanding of the ease or difficulty of the reauthorization process. If it's easy, we get to paid shipments quickly. If it's going to be difficult, the team can act faster with better information to solve any issues. Even though we still provided temporary free product for many patients during the first quarter reauthorizations, the faster actions in the quarter meant that paid shipments were within 1% of fourth quarter 2023 paid shipments. This was above our expectations. As for customer demand, we had another very strong quarter for new patient prescriptions. In fact, the last two quarters have been the best consecutive quarters for demand since the six months of the launch in 2021. Patients and healthcare providers continue to understand and gain confidence that they can get great efficacy and convenience with Orlodeo, all with just one capsule once a day to prevent HAE attacks. We also continue to strengthen the brand by presenting new evidence showing the real-world impact of Orlodeo. At Quad AI in February, we showed how well Orlodeo is controlling HA attacks, regardless of prior therapies or baseline attack rates. Patients switching to Orlodeo from other HA prophylaxis therapies, for example, maintain and even improve long-term attack control, reaching a median rate of half an attack per month. Patients attack-free at baseline remained attack-free on Orlodeo. Later this week, we will present new data at the ISPOR conference in Atlanta, demonstrating that patients initiating Orlodeo experience significant reductions in overall healthcare resource utilization, a finding that will be very meaningful to payers. We are well positioned to provide frequent health outcomes and economics updates with large and growing cohorts that already include hundreds of patients. These new data will further support the growth in customer demand for Orlaneo for many years to come. The increasing customer confidence that we're seeing in the US is also happening in the rest of the world. Patient growth in Europe was strong and consistent in the first quarter. And recent launches in Spain and Italy are already adding to this trend. Finally, our Biochrist Japan team is now fully in place from the start of 2024. and we are encouraged by the early signs of their impact. The overall trends in real-world evidence, customer confidence, and patient growth continue to point to $800 million in peak U.S. revenue with sustained peak global revenue of $1 billion. I'll now hand over to Helen to provide an update on our pipeline.

Thanks, Charlie. Our research and development teams are busier than ever as we are rapidly approaching our next major pipeline milestones which include advancing multiple programs into the clinic starting later this year and filing for pediatric approval with Orladeo. Let's start there. I'm pleased to share that we've completed enrollment in the pediatric trial with Orladeo, which includes extending dosing in children down to two years of age. This means we're on track to submit for pediatric registration as planned in 2025. It also means we are even closer to providing the first oral prophylaxis therapy to children with HAE. It's been remarkable how quickly our pediatric enrolled. We believe this reflects the demand for an oral therapy as prophylaxis of HAE attacks in children. It has the potential for this to be a transformative option for both children and their parents, a pediatric formulation made of granules that can be sprinkled on soft foods or taken with a glass of water. We're excited to be so close to achieving this goal of bringing Orladeo to children under 12, and we look forward to submitting for registration next year. Turning to our next clinical program, our factor D inhibitor, BCX10013, we continue to progress the ongoing proof of concept trial, and we expect to either partner or discontinue the program later this year, as planned. Up next, we have two pipeline programs that will enter the clinic within 18 months. These are BCX17725 for Netherton syndrome and Avoralstat for diabetic macular edema, or DME. We are on track to begin a clinical trial with BCX17725 by the end of this year. This is a fusion protein with very high potency inhibition for KLK5, and it has the potential to be a best-in-class product, providing disease-altering treatment for people with Netherton syndrome. Netherton syndrome is a rare, lifelong genetic disorder that often presents in infancy with red, scaly, and inflamed skin. Patients require chronic care to protect the skin and monitor for lifelong susceptibility to inflammatory and atopic conditions. Netherton syndrome can be life-threatening, especially during infancy when neonates are vulnerable to dehydration and recurrent infections. Currently, there is no approved treatment for Netherton syndrome. and it's our goal to deliver a targeted therapy for these patients. Next into the clinic will be a vorostat, our plasmacalocrine inhibitor, in development for the treatment of diabetic macular edema, or DME, which is on track to initiate a trial in patients next year. Our goal here is to improve vision in patients with persistent DME despite the use of VEGF inhibitors. At least a third of patients with DME have continuing symptoms and even worsening vision loss when treated with EGF inhibitors, which may be because plasmacalocrine is a contributing cause of disease. The need for additional therapeutic options is real. We're working with ClearSide to deliver a viral stat to the suprachoroidal space in the eye in order to achieve sufficient exposure in the right location to interrupt the pathophysiology of DME in the retina and stop swelling in the back of the eye. Based on the preclinical and safety data we accumulated with the Boralstat when we studied it in the HAE program, we are in a position to move quickly into patients with DME with our first clinical trial next year, so we can evaluate for proof of concept directly in patients. Right behind these two programs, our discovery programs for targets across the complement system are also advancing. The three programs underway include our protein therapeutic complement inhibitor, targeting all three pathways, the classical, lectin, and alternative pathways complement, and our oral C5 and oral C2 inhibitor small molecules. We are on track to have both the oral C5 inhibitor and the protein therapeutic multifunctional complement inhibitor advance into IND-enabling studies later this year. So in summary, we continue to progress well towards our goal of delivering inhibitors for every pathway in the complement system. Overall, the depth and breadth of our pipeline provides balance and great potential with a diversified set of molecules moving forward. This allows us to increase the likelihood that our pipeline today will produce our next drug in the market tomorrow. We are excited the pipeline is now advancing into the clinic with multiple programs. Next, I'll turn it to Anthony for a financial update.

Thanks, Alan. You can find our detailed first quarter financials in today's earnings press release, and I'd like to call your attention to a few items. Total revenue for the quarter was $92.8 million, $88.9 million of which came from Orladeo, with the remaining $3.9 million coming from Rapavab sales. That puts Orladeo trailing 12-month revenues at $346.4 million, with Q1 revenue increasing 30% over Q1 of 2023. Of the $88.9 million of global holiday revenue sales, $80 million came from U.S. sales with the remaining $8.9 million or 10% coming from ex-U.S. sales. The 30% year-over-year increase in sales was primarily driven by the strong underlying patient growth that we have continued to see quarter-over-quarter. The $4 million improvement in Q1 performance versus our previous guidance of $85 million was primarily driven by the efforts of the commercial team to improve and accelerate the reauthorization process. That's $4 million that last year we would not have been able to capture until Q2, but this year the team managed to accelerate the timing and achieve it from quarter one. For Q2, we expect to achieve revenues of approximately $97 million. And as Charlie said, we've revised our full year revenue guidance to the higher end of the range between 390 and $400 million. Operating expenses not including non-cash stock compensation for the quarter were 93.6 million, an increase of 10.4 million over Q1 of 2023. Included in this are 1.3 million of one-time expenses related to the R&D structuring at the beginning of the year. Full-year 2024 guidance for OPEX is unchanged at between $365 and $375 million. With revenue up $24 million year-over-year at $92.8 million and OPEX up $10.4 million year-over-year at $93.6 million, we continue to see improved margin accretion and our operating loss for the quarter, not including non-cash stock comp, was less than $1 million. Cash at the end of the quarter was at $338.4 million dollars. and net cash utilization for the quarter was 52.4 million. Q1 is historically our largest quarter of the year for cash utilization. For context, last year's Q1 was responsible for over 50% of total cash utilization for the entire year. Including Q1, this year we had 3.2 million related to the R&D restructuring and 6.9 million related to royalty payments to OMERS. This is our first quarter of making such progress, cash payments to OMERS, and as a reminder, while the royalties are considered a debt instrument for GAAP purposes, they cannot be called and ultimately should be considered more of a long-time liability than true debt. Additionally, with the revised guidance for full-year or all-day revenue, this will result in an improved blended royalty rate, as more revenue will fall into the above $350 million tier, where royalties are at a reduced rate of 7.5%. Cash utilization will decline in the remaining quarters of the year as it did last year, closer to an average of 10 to 12 million per quarter, and we expect to end the year with above $300 million in cash. It's great to see the continuing strong performance of Orladeo. The commercial team did an outstanding job to improve our performance during the reauthorization process, an improvement that we'd hope to continue and build upon in next year's quarter one. This strength in revenue performance supported by continued strong underlying patient demand is what drives the revised full-year revenue guide between 390 and 400 million. And with full-year OpEx remaining consistent prior guidance, we are in an even stronger position to deliver an operating profit this year when excluding non-cash stock comp. We will continue on our planned path to near-term profitability that we shared earlier in the year, approaching quarterly cash flow and EPS positivity late next year with full year cash flow and EPS positivity in 2026. All while continuing to advance our pipeline at full pace without the need to raise additional capital to get there. Operator, we'll now open it up for questions.

We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Jessica Five with JP Morgan.

Please go ahead. Hey, this is Nick on for Jess. Congrats on the quarter and thanks for taking our questions. Two from us. You mentioned the past two quarters are the most new prescriptions in the U.S. since the first two quarters of the launch. Can you maybe provide some additional details on how that trend is looking so far in 2Q and then maybe one on ex-U.S. revenues? I know they came in at 10% this Q. You've talked about them being lumpier than the U.S. How should we expect that growth ex-U.S. business this year? And at what point could that become less lumpy?

Charlie, why don't you take the first one, and Anthony, take the second one.

Sure. I'm not going to comment yet on Q2, but other than two consecutive quarters of really great prescriptions, we've talked before about all the market research that we do with physicians. They continue to expect to grow Orlodeo prescriptions by about 30% over the next year. So we would expect this kind of demand to continue.

Hey, Charlie, is it worth spending a little bit of time talking about the confidence that you're seeing in physicians and patients at this stage since the approval?

Sure, yeah. Like I said in my prepared remarks, as physicians have gained more and more experience and patients as well, they see that this drug is much more than just a convenient oral therapy. They see that Orlaneo is a really effective therapy and once they know that they can expect the high efficacy and the convenience together, it just gives them more confidence in prescribing. Physicians know that the majority of patients would prefer an oral therapy, and if they can get a really effective oral therapy, that makes them want to prescribe more. And I think that's what we're seeing now three-plus years into this launch. So, Nick, with that confidence, we just don't see it letting up.

Anthony?

Yeah, so for XUS, yeah, definitely. By the nature of how we sell into the ex-US markets, there's always going to be some lumpiness. Last year, we had about 11.5% of our total revenue come in from ex-US. I would expect something similar this year. I mean, if it's not there, it'll be due to US overperformance as opposed to ex-US not being where we expect it to be. Ultimately, we would expect ex-US sales to continue to increase over a year until we hit peak.

And just to add, too, on the lumpiness, that really is, it's just based on how we distribute. It has nothing to do with customer demand. What we're seeing is physicians are gaining the same kind of confidence that I described in the U.S. and we expect that to continue.

Great. Thank you. The next question comes from Mari Raycroft with Jefferies.

Please go ahead. Hi, congrats on the quarter and thanks for taking my question. In your prepared remarks, you talked about your patient services team and investigations early in the first quarter that led to categorizing reauthorizations as easy versus difficult. Can you talk more about what makes their reauthorizations easy versus difficult and how you plan on building upon your learnings for the rest of the year with that?

Sure, Maury. You know, with this kind of rare disease therapy, Payers are always trying to make things a little bit difficult, but it's the kind of thing that I've described before, which is they want a full patient history, they want lab tests, they want all the information they can get. And sometimes when the payers already have this information, they can make it pretty quick to get to the reauthorization. but it's kind of in the payer's interest to throw as many speed bumps as possible. So even if we've provided it before, sometimes they'll ask for it to be provided again. And then there are some patients who just have more complicated histories, and those are the bigger challenges. But our teams had great success in getting all types of patients approved. So sometimes it's quick, and sometimes it just takes a little bit of time. Everything that I see, though, gives me confidence about the 85%. paid rate at peak, it's just going to take us a few years to get there.

I think the other piece is Charlie made a decision a little over a year ago to change the model and improve this reimbursement and the support services around it. We're starting to see the fruit of that, and I think we'll continue to see that as this year progresses and future years. So it's a great, great signal, great signal. Got it.

maybe just a quick question if you can comment on um the latest that you're seeing with gross to net and with um the price increase though that you took in january is that um something that we should expect going forward for the next couple years the first one you take the second yeah on the gtn side so for reimbursed product you know we've historically had 15 to 20 percent and much like last year q1 is at the higher end of that range closer to 20.

For the remainder of the year, based on the speed at which Charlie's team got through the re-auth process, we'd expect it to come down and be at the lower end.

And, Maura, this year we did, at the beginning of the year, we had a 5% price increase, and we expect to net about 3.5% of that. And as far as growth to the $800 million at peak in the U.S., all we would expect is very modest price increases as part of that build towards the $800 million increase.

Got it. Thanks for taking my questions.

The next question comes from Tahzeen Ahmad with Bank of America. Please go ahead.

Hi, guys. Good morning and thanks for taking my questions. Can I ask about 1013? Any more color on when you expect to make a final decision on that asset and are you going to be presenting any more data if you do intend to move forward with that? And then I just wanted to ask a question about guidance. And based on where you are, it's still early in the year. Is it possible that you could revise the upper end of guidance higher as the year progresses just based on trends that you're seeing so far? Thanks.

Yeah, on 10-0-13, as we said at the beginning of the year, the goal is either to partner it, or if we can't, then we'll stop the program. And so the next thing that you'll likely hear is whether or not we've decided to partner the drug. And then on guidance, we've adjusted the bottom up in the range, and when we're confident to adjust it further, we'll let you know. But for right now, it's moving the bottom up.

Okay, was there a follow-up to your question?

I think both were answered, thanks.

Thank you. The next question comes from Serge Belanger with Needham and Company. Please go ahead.

Good morning. Thanks for taking my questions. I guess for Charlie, you mentioned two strong quarters of patient growth exceeding the first two quarters of the launch. Can you give us just a little more color on that and maybe how it compares on a year-over-year basis? And then with the success of the reauthorization process, it sounds like we're not going to see the usual seasonality trends. I'm curious how you think about your long-term target of 85% paid scripts. Is that still the target, and does that move up the timeline to hit that target?

Thanks. Thanks, Serge. So just to clarify one thing, the last two quarters were the best two quarters since the first two quarters of launch. So the first two quarters were just slightly better, but I think what it shows is that there was no just, you know, there's no bolus of patients early that we got and then demand falls. demand is actually building over time as customers gain more confidence, like I was saying in one of my previous responses. And then the 30% growth in revenue year over year, I think kind of speaks for itself at this point in launch to be growing that strongly is impressive. As far as the Q2 seasonality, as Anthony was saying, we would not expect as big a jump this year. We're guiding to $97 million in Q2. And we would expect that same trend, I think, in the future, where we're going to get more revenue in the first quarter just through more effective reauthorization processes. And then as far as the growth to 85%, that underlying improvement in the rate of paid As I commented before, it's going to take us some years to get there. All of these improvements that we're making with adding to the team, getting better and better each year going through this process, tells me we're going to get there. And the bigger jump, the bigger opportunity would be next year with the IRA rolling in, and hopefully that helps us get more Medicare patients to paid therapy as the maximum out-of-pocket goes to $2,000. But the overall growth to 85% is going to be a multi-year process.

Thank you. The next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead.

Hi, everyone. This is Nevin on for Brian. Congrats on a good quarter. I just have a couple questions on SG&A and some of your strategic initiatives to maybe accelerate some of that. Can you speak to some of those, you know, whether you have any sales acceleration initiatives planned to drive any increased uptake either in the U.S. or ex-U.S. as well with some of the expansions and some of the geographies, ex-U.S.? And then are you in – fourth quarter you had guided towards an increase in SG&A of about $20 million. Is that still the case for 2024? And could we expect the patient services team to be in place throughout the year, or would this be something that, you know, you would add to the team seasonally as well near the end of the year, maybe add to the team to help with the re-off

Charlie, maybe just talk in general about where you're at with the build of your team, and then Anthony can talk directly on some of it.

Sure, and I'll also talk about some of the specific initiatives that Ned had asked about. So the investments we made last year were to, like I said, just to improve the efficiency and effectiveness. We're always looking to make improvements at the margin. If we see an opportunity, we'll add a little bit. We don't expect any major adds to our team at this point. It'll just be kind of marginal additions, particularly as our patient base grows. Our patient services team will grow slightly as the patient base grows. But that's not a seasonal growth. That's kind of long-term investment in the team. And then we're always looking to strengthen the brand with additional data and additional initiatives. So we'll continue to look for those opportunities, like the real-world evidence that I described in my prepared remarks.

In terms of where we are versus what we had talked about previously, I'd expect about a 20% increase in SG&A year-over-year. But again, most of that is broken down into kind of the full-year impact for the increases that Charlie's team did where you had partial impact last year. And then for the ex-US side, yeah, there'll be smaller increases, but I would think about it far more in terms of how the team is focusing on the idea of margin accretion. So the investments that we are making, the investments that we continue to make, are going to be significantly less than the revenues that are generated as we get towards peak. And so I'm really excited to start to see, you know, that margin accretion and its role in getting us to and through profitability.

Got it. Thank you. I just wanted to clarify, you mentioned 20% increase year-over-year?

Sorry, $20 million. Okay, thank you.

Evercore ISI. Please go ahead.

Hi, congrats on a good quarter. Just a couple points of clarification. For your outside, like OUS revenue, and you said it was about 10%, does that include the Japanese royalty or no?

Yes, it does include the Japanese royalty.

Okay. And then... What were gross to net in the quarter, and maybe you can comment on how they'll evolve over the course of this year?

Yeah, so gross to net on the reimbursed side here in the U.S., closer to 20%. So, again, historically guiding to 15% to 20%. That includes the reauthorization impact, the copay assistance impact, the reset of that, and then moving towards the latter part of the year, it'll normalize closer into that 15% range, but it'll average us out for the year in the 15% to 20%. Okay.

And then other revenue, how much of that is Japanese revenue and how much that is?

Rappabab or other stuff?

Could you clarify?

Yes. Revenue is all Rappabab. Yes. So 88.9 of it is Orladeo and then 3.9 is Rappabab. If you're asking for a specific split of product versus other revenue, we don't generally give that. But listen, Rappabab revenue for the most part is inconsequential, especially as Orladeo revenues get into the point where it's almost $100 million a quarter.

Okay, but that doesn't include Japanese revenue in that line there.

The 88.9 does. The 88.9 does include Japanese revenue. Okay, got it. And then any inventory changes in the quarter? No, we continue to be laser-focused on ensuring that we have significant quantities. The cost of sales is really, really low, and so our team does a great job of making sure that we have enough for all of our territories.

Okay, great. And then just finally, can you maybe just talk about the pediatric expansion opportunity and just kind of qualify that in terms of the potential upside there?

Sure. I think the first point is, as Helen pointed out, there's just a huge need amongst kids to have an oral therapy. It's not just the kids, it's the parents. So I think that this is a very highly anticipated product launch when it comes from the market. We think there are about, in the U.S., about 500 kids who may be in the consideration for prophylactic therapy. It's an evolving space because there haven't been prophy therapies available for kids before, and then to have the first oral, it'll change. So it's up to 500 patients for prophylaxis. And then the other piece is just the halo effect, which is another way to introduce Orlodeo to physicians and to families, to patients. And so we expect it to be an important for us.

And as Helen said in her remarks, when you enroll faster than you thought, that's usually a really good sign that you've got something that people want, and that's exactly what happened.

Okay. Great. Thanks.

The next question comes from Stacy Koo with TD Cowan. Please go ahead.

Thanks so much for taking our questions and congratulations on the progress. So we have a few follow-ups. So first, regarding your Q1 outperformance, what do you think is contributing to this new persistent growth? Just characterize these patients a bit more. Is it coming from new prescribers versus concurrent prescribers? Is this from kind of your patient activation kind of activities? So that's the first question. And then the second is around your long-term expectations for the Japanese launch of Orlodeo. Can you just speak a little bit more about you're seeing um so far in early days and how you feel comfortable kind of long term um for that for that opportunity and then last um just on 10 0 13 for the partnership is the team waiting for the full 24 week results before engaging in discussions and and just to confirm you all would still be getting those results um in the middle of 2024 but you do not anticipate disclosing data to the street thanks so much hi stacy so in the the first question just in terms of the color on the new new growth

It's very similar to what we've seen before. So we're getting prescriptions from existing prescribers. We're always adding new prescribers as more become aware of Orladeo and gain confidence. The mix of patients is also very similar, the roughly 50% switching from other prophy and the other 50%, best we can tell, being naive to prophylactic therapy. So very consistent, and as I mentioned earlier, consistent to what physicians expect to do in the future. They see a lot more growth coming over the next year. As far as Japan, we think still that there are fewer than 1,000 patients who've been identified in a market that could be 2,500 to even 3,000 HAE patients. So what the team is focused on right now is driving use of prophylaxis and oral prophylaxis within the the diagnosed patient community, and just building awareness about Orlodeo. Longer term, we think that as we're there with Orlodeo, other manufacturers are there with other prophylaxis products, there will be more patient diagnosis. And so we expect this to be a growing market for the next five or ten years. We're very enthusiastic about the opportunity in Japan.

And then, Stacy, on 10.0.13, yes, we expect the data the middle of this year, but what matters, since we're not advancing it, we're seeking a partner to advance, it's what do they think about the data at the end of the day. And so that's where we'll focus our attention.

Understood. Thank you so much.

Again, if you have a question, please press star, then 1. The next question comes from Gina Wang with Barclays. Please go ahead.

Thank you. Maybe just one regarding the Japan, since we have quite a few questions on Japan market. What is the price there? Is that also 30% to 50% discount of the U.S. price, similar to Europe price? And the second question is regarding the pediatric trial. I notice it is a single-arm study. What data could be approvable based on FDA feedback?

Charlie, you take Japan price, and Helen, take the... Gina, the Japanese price is actually the second-highest price, oil and oil price, in the world. So at the moment, and then of course it's subject to exchange rate variation, but at the moment it's close to $200,000 per year. So it's higher than our European prices.

And then Helen. The question on the pediatric trial, it is single arm and that's fairly standard now for what's called extrapolation of the data. The point is to match exposures in the pediatric population and with the exposures that are known to be effective in the adult population. So it's safety and PK, and that's what will be submitted to the agency.

I noticed you do have also attack rate collection. Will FBE also consider that data point, any, like, say, threshold that you have to achieve?

So attack rate's always collected when you're following patients, and we know the patient's doing well. That'll be submitted as part of the data set. but the decision will be based on safety and the exposure.

Okay, thank you.

The next question comes from Francois Briseois with Oppenheimer. Please go ahead.

Hi, thanks. In terms of the pediatric importance here, you talked about up to 500 patients, but is there a scenario where you'd ever expect a pediatric to be on this and then turn into an adult and maybe change treatment option? I'm just wondering, too, if you can remind us all of the competition on the pediatric front?

I think what we would see is that patients who, kids that need to start on prophylaxis, an oral is going to be the best option for them, just for obvious reasons. And this is a lifelong disease, so we think there's an opportunity for these kids to be on Orlodeo for a very long period of time. And then, as I mentioned earlier, just the family aspect of it, too, as a genetic disease. Usually there is a parent or often a sibling, other family members in the household. And so it's an opportunity for whole families to become more aware of the benefits of Orlodeo. So we would expect them to stay on for the long term.

Understood. Thank you.

The next question comes from John Williams. Wolopin with JMP Securities. Please go ahead.

Hey, thanks for taking the question. One on your market research, which has been seemingly accurate in the past. When you ask about prescribing the next 12 months, wondering if you actually ask longer term as well about ultimate usage, how that factors into your growth projection, then also it seems to be reflective of the uptake we're seeing. Do you ever have to expand who you're asking and what you're asking about to get more insights into what the trajectory looks like three, four years down the line.

Thanks for the question, John. We absolutely do look at that longer term and ask them about the longer term. The growth in the next 12 months, that's the quarterly survey that we do with 60 to 100 physicians every quarter. Then we use that information plus other studies once a year to build a much longer-term model where we also incorporate everything that might come in the future, and we ask physicians their opinions of those products, what they think they will use, and then that all goes into a much larger market forecasting model to predict the future. It was very accurate in our first year of launch, and every year our team updates this model, and so we have a lot of confidence in our future predictions, and it is That is where our billion-dollar peak revenue comes from. It comes from that model that incorporates all of the forward-looking market research.

And then when this year do you guys do that annual revamp, and will you guys let us know the results?

We won't let you know if anything changes. We do it once a year around the middle of the year, and – Yeah, our goal is to be accurate in all of our forecasting. So if we see anything different, we'll definitely let you know.

Got it. Thanks, Charlie.

Your last question comes from Chris Raymond with Piper Sandler. Please go ahead.

Thanks for squeezing me in. John, you've been pretty open in the past when folks have asked you guys about strategic interest and sort of inbound interest. And I think it's pretty clear now, by now, that there's a lot of buoyancy here, if you will, for maybe lack of a better word, to Orla Deo's uptake. I guess any discernible change in terms of frequency or maybe tenor of the inbound calls that you guys have had from strategics? Thanks.

Yeah, Chris, I mean, you know I can't talk about specifics and volume or changes, but the answer about our willingness to entertain those remains unchanged. We're a public company, and we have shareholder interest in our minds, and if someone is interested, we'll take the call. So no change there. Thank you.

This concludes our question and answer session. I would like to turn the conference back over to John Stonehouse for any closing remarks.

Yeah, thanks again for your interest in our company. We are off to a really, really good start to this year, and we're super excited where this will lead us to in terms of Orla Deo trajectory and advancing the pipeline. So we're focused on continuing this momentum throughout the year and look forward to updating you as we have new information. Have a great day.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.