BioCryst, and we're going to do a fireside chat format. So maybe for those who are new to the story, Charlie, if you wanna give a one-minute intro to BioCryst. Sure, great. Thanks, Maury, and thanks for having us. And just before I start, I'll be making some forward-looking statements. Those statements have risks, and you can learn about those risks on our website. BioCryst is a biotech company based in Durham, North Carolina, and we have Discovery Center of Excellence in Birmingham, Alabama. And it's a really exciting time for us because we have ORLADEYO, which is a once-daily oral therapy for hereditary angioedema, that is on track for $1 billion in peak global sales. We also have a really interesting pipeline of molecules that we think have the potential to generate the next billion-dollar product. And then finally, we are on track in 2026 to be profitable on a cash flow and earnings per share basis, so independent of the capital markets, and so it's a great time for us. Great. Yeah, it's a great intro, and you've got the commercial product, ORLADEYO. Revenue in first quarter 2024 beat expectations, and the stock responded favorably to that. For your 1Q sales, revenue was up 30% year-over-year, and based on assumptions, we have the number of patients on your free drug, we estimate it's about 30% of that. And revenue could increase, representing approximately 25% of total patient number growth through year-over-year. I guess, maybe talk a little bit about how you're seeing this, and is this consistent, or what? Is this consistent with the numbers that you're thinking? Yeah, and I think the first thing to say, Maury, is that patient growth really is driving our revenue, obviously. And the last two quarters, so Q1 of this year and then Q4 of 2023, were the best two quarters for patient demand that we'd seen since the very first two quarters of the launch back in 2020. So we're obviously very excited about that. The 25%—your estimate of 25% patient growth, it's close. I'd say it's sort of between 25% and 30%, driven by that patient demand. And then the other thing that we can talk about more is we are working to get that level of paid patients from the low 70s, where it ended last year. Over the next few years, we expect to get that up to about 85% paid. Got it. Okay, makes sense. And given the growth in patient numbers for first quarter, are you seeing anything surprising for second quarter? And can you say what the sales number for second quarter will be? I think in the past, you guys have been pretty transparent about that. And, and for the year, you're guiding to $390 -$400 million. What are your assumptions going into third quarter and fourth quarter? I won't comment on Q2 specifics at this point, but like I just mentioned a minute ago, the demand has been really strong in the last two quarters. So I think what we're seeing now is three and a half years into the launch, physicians and other healthcare providers and patients are really starting to see that ORLADEYO is a highly effective drug. So it's not just convenient, it's really very effective, and so that's leading to more and more prescribing. For Q2, we have guided to $97 million in global sales, and so what that means for the rest of the year with the $390 -$400 million is we will be hitting our first quarters of more than $100 million in sales, and we expect that this consistent patient growth of at least 200 net patient growth per year will continue for the rest of this year and several more years through the rest of this decade. Got it. Okay, and behind the 1Q commercial performance, you commented that the U.S. commercial team completed reauthorization faster than expected. Can you give us an update on the percentage of patients on free drug now, and where do you think it is trending toward by the end of this year? We ended 2023 at 71.5%, we're on paid versus long-term free product. What we, as I mentioned a minute ago, we expect that to consistently improve incrementally over the next couple of years. And the real thing that in Q1, the real success was Q1, about half the patients end up going through a reauthorization process, and this year, we just did it faster, more efficiently. So what that meant is in normal years, we give away some free product while we're going through the reauthorization. We had to do less of that this year, so we were able to generate more Q1 revenue, and what that means is we expect the Q2 revenue to jump, but not as dramatically as it has in past years because we've already captured a lot of that revenue in Q1. Got it. And I don't know if you're providing more granularity on just the, the numbers of patients, and, and so I guess, can you break down the total number of patients that are on drug and then the number of patients on free drug, and say what proportion is on commercial insurance versus Medicare or Medicaid? We ended up having given specific numbers for Q1. We did mention that we ended last year with 1,004 patients who had reached paid or long-term free product, and then last year, we added a net 321 new patients. So above that, 200 per year that we need to get to our peak of $1 billion in peak sales. Sorry, what was the second part of... Oh, the payer mix. So our payer mix has been really consistent since launch. It's about 60% commercial, 20% Medicare, and the remaining 20% is mostly Medicaid, with some other smaller government payers. Got it. Maybe talk about your plan and on how you can improve these numbers, and how do you, you're setting expectations for the rest of the year. I guess, are there ways to optimize going forward? Yeah, I think the thing that we're working on to get that paid rate above the low 70s, number one is working with healthcare providers to provide all the information, the complete information on prescriptions that payers require. So that includes lab tests, it includes patient history, justification. We've been expanding the prescriber base for ORLADEYO so rapidly and successfully, that a lot of these physicians don't have as much experience going through this process, and the payers will slow things down if it's not complete. So that's the number one thing that we can do. We've contracted with all the big payers and PBMs, but there are a lot of smaller payers, too, that we're starting to work on and make sure that they understand the value of ORLADEYO and why they should pay for it. Got it. Okay. And, how do you expect the IRA to impact the insurance dynamics next year and onward? And do you expect the IRA to affect discount and gross- to- net in the long term? We view the IRA in the near term as it's a good thing for patients. The Medicare, as I said, is about 20% of our business. Historically, Medicare patients got to paid therapy at about 80%, but in recent years, it's been harder for Medicare patients to afford their co-insurance. So even this year, with the IRA partially implemented, the max out-of-pocket for patients is about $3,250. That's still a lot of money for somebody on Medicare. Next year, that cap goes to a maximum of $2,000, which will make the co-payment more affordable to patients and help them get the assistance that they need. As patients have struggled with that affordability, what we've been able to do is put many of them on long-term free product because we wanna make sure that they're not suffering from their clinical outcomes. So with the full implementation of the IRA next year, we hope to get many of these patients back toward the 80% payment rate. In the last couple of years, it's dropped to 50% in the Medicare segment, and that's all because of patients affording their co-payment. Got it. Oh, and sorry, gross -to- net. Longer term, we expect as we as a manufacturer have to pay more of the catastrophic phase. Longer term, we do expect that to affect gross- to- net a bit. We've guided to gross- to- net being about 15%-20% on paid patients, and so it would probably move up into the higher end of that end of that range once the IRA is fully implemented. Got it. Okay. And, let's talk a little bit about the commercial dynamics. For HAE patients today, they already have a few options for prophylaxis, but ORLADEYO is the only oral option. What are your latest thoughts on how you expect the market dynamics could look when there are more treatment options in long interval injectables on the market as well? And this is, it— HAE is a pretty incredible story, that there already have been eight targeted therapies approved between prophylaxis and acute, and as you mentioned, there are more to come. So for a rare disease, that's pretty amazing and great for patients. What this means is most patients are under pretty good control, and they're... What they're looking for, what's really key for a new brand, is to have something that is really differentiated and meets a need that was previously unmet. So for ORLADEYO, as the only oral therapy, that's a big deal for patients to be able to control their disease with just one pill a day versus doing it with injectable medicines. For new drugs coming, the real key is gonna be what is that differentiating point? And we think that patients are doing so well on ORLADEYO now, the ones who are doing well are gonna stay on, and we've got a big head start in the market. Got it. And, and based on some doctor feedback that we've gotten, it seems like there's a lower barrier to switch patients from other therapies to ORLADEYO, but there could also be a low barrier for patients to try out, new therapies as well. What are your latest thoughts on, patient stickiness, and what are you working on to increase brand awareness and, and loyalty? Patients are really sticky across, across the board. As I just mentioned, if you're doing really well on ORLADEYO, what we're seeing is patients are getting down to about half an attack per month, and our long-term clinical data shows that patients got a 91% reduction from their baseline attack rate. So they are doing really well. If you're getting that kind of efficacy on one pill a day, you're gonna stay on that therapy. I'm sorry, the second part of your question? Just ways to increase- Ah, yeah ... brand awareness and loyalty. So actually, just this week, if you go to ORLADEYO.com, you'll see our new campaign, which is focused on with ORLADEYO, you get both great efficacy, as I just mentioned, and convenience. It's not an or, it's not a trade-off. You can have efficacy and convenience, and this is a big focus for us now because we're seeing patients get great efficacy, and of course, a once-a-day oral is very convenient for patients. Got it. Makes sense. When it comes to safety, when we track the FAERS data, the FDA safety data that's out there, it highlights that there's a lot of injection-related AEs with Takhzyro and Cinryze, and I think your GI AEs have been consistent over time. How do you leverage safety data you get from your real world experience, data that you're collecting, whether it's from competitors or from your own drug? I think you point out one thing with ORLADEYO that does happen for some patients is GI side effects. It's ORLADEYO's proven to be a very safe and well-tolerated drug, but that's the one thing that can happen. What we see in our clinical trials, we see in the real world, is that if you do experience GI effects, those tend to happen early in therapy. They tend to go away after a few days or a few weeks and then not return. And so with healthcare providers and with patients, the real key that we focused on for the last several years is setting expectations. It's important to let the patient know that this could happen. If it does, it's likely to go away. This is why you should take ORLADEYO with a meal, which can help mitigate that, and that's worked really well. What we hear from doctors is this issue about GI is not a big deal. They're very comfortable with it now, and I love the fact that you look at the FDA data because I think that kind of underlines that point. It's turned out it's there, but it's not a big issue for most patients. Got it. In the FDA data, there's also the injection-related AEs as well from some of the competitors. Yeah. And so with the totality of the story, and I think you guys are collecting real-world data as well, how can you leverage that just with educating doctors and patients going forward? Yeah, I think what we do is, you know, back to the convenience of an oral, that is part of the benefit of ORLADEYO, not having to deal with regular injections. It's not so much that most patients are afraid of needles, it's just that there's a burden to doing that for many patients over time. There's also a burden of if you want to travel, you have to travel with all your injections, travel oftentimes with refrigeration for those products, and ORLADEYO is just a lower burden. What we hear from a lot of patients is, when they can control their disease with just one pill a day, and they have that kind of freedom in their life, they can almost forget that they have HAE when they're under good control, and that's what we focus on with both doctors and patients. Got it. Makes sense. In one of your recent updates, you said that ORLADEYO, the pediatric study is fully enrolled with the sNDA planned for 2025. Can you remind us how the pediatric patients are managed today? In the past, you said that there are approximately 500 pediatric patients in the U.S. How do you think ORLADEYO market penetration could look like for this population, and what could the ramp-up for the population look like once you get this expanded label? Yeah, we're very excited about this. It's. As you point out, it's a relatively small population, about 500 kids in the U.S. with HAE, so children under the age of 12. We think that you know, maybe about half of those might need prophylaxis therapy. And what's happened is in recent years, where targeted therapies have started to become available to children, a lot of doctors are starting to rethink how they treat kids with HAE. Fortunately, most kids who do have HAE tend not to become symptomatic till around puberty, but if they do become symptomatic earlier, it's a big deal. And if you can control you know, for a 5- or 6-year-old who's having attacks, if you can control their disease, it can kind of set their life on a different and better trajectory. And for kids, the benefit of an oral, not just for the kids, but for parents, it's pretty clear. And so we've had a lot of parents really excited about this opportunity to have an oral therapy, and so we look forward to that filing in 2025. Got it. And anything more you could say about just how you'd expect the expansion into that opportunity to look like? I mean, I think, as I said, the benefit of an oral for kids. Overall, about 50% of our patients have switched from injectable therapies. I think with kids, that switch is just gonna be easier. Got it. Okay. And, ORLADEYO's got a great IP, patent life, but in rare diseases, we've seen sales plateau after about 3-5 years of launch. How do you think about the drivers that get you to $1 billion in peak sales by 2029? Yeah, as Maury mentioned, we have composition of matter on the base molecule to 2035, and then the salts into 2039. So, we feel great about those patents, and that gives us, once we get to peak around the end of this decade, that's a long runway of additional sales. So the building blocks of that in the U.S., we expect to get to about $800 million in peak sales. The first building block of that is adding, as I mentioned earlier, adding about 200 net patients per year. We added 321 last year, so we're well on track, doing that through 2028. So more in the earlier years, it might drop a little bit lower in later years. That adds about $300 in annual revenue above what we did last year. The next block is, that I also mentioned, was getting the paid rate from about 72%- 85%. That adds another $100 million in annual revenue, and then a modest annual price increase. This year, we had a 5% price increase, where we net about 3.5 out of that 5. We don't even need a price increase of that size. That adds about another $100 million, and then we expect $200 million in sales in other markets: Europe, Canada, Latin America, Asia, and we're off to a really good start with that. So $200 million will come from other global sales. Got it. Makes sense. Competitor, Takhzyro's first quarter 2024 revenue increased 17% year-over-year, which is a positive indicator since this drug has been on the market for so many years. Where do you think the Takhzyro growth is coming from, and how does Takhzyro's ongoing commercial program function as a playbook for BioCryst? What we see is that their US sales are really flattening at this point, but where they're getting their growth is everywhere else. I think they announced in Q1 that they're commercialized in 55 countries. This is a global disease, and so we're following that playbook. And the global growth takes longer. You have to get the registrations, you have to go through the market access, but there's a need for targeted therapies everywhere, and that same benefit of an oral therapy applies globally. So we're kind of following that playbook. Got it. Makes sense, and wanted to talk about some of your pipeline programs as well. With Factor D, you're on track to have data from the PNH program middle of this year, and it seems like you may not share the data with the public right away. Do you have the data in-house, and is there anything else you can say about timing for when you would provide some sort of an update on whether you, you decide to partner or discontinue? Yeah, this is our oral Factor D, BCX10013. We are on track with a proof of concept in PNH. We're on track to have data from that study in the middle of this year, and we've noted that at the beginning of the year, we'd met with some companies that could be interesting partner—could be interested partners for this. The reason we want to partner this drug is because there are so many places, if it turns out to be a successful drug, so many different indications that could be pursued, and we think that a partner with more resources could just go broader, more quickly than we could. We'll either partner it in the second half of this year, or if we're not able to do that, we will, we'll end this program by the end of this year. Got it. Makes sense. And last year at your R&D Day, you disclosed an interesting pipeline of new programs. Both the Netherton and DME programs can move into the clinic to get to data updates next year. Starting with Netherton, can you remind us what the target is, where it sits in the disease pathology, and has anyone else attempted to do what you guys are doing with this disease setting? Yeah, so Netherton is a ultra-rare genetic disease that patients have a defect in the SPINK9 protein that regulates KLK5, which is a tissue kallikrein, that in turn governs the turnover of skin. So what for kids, infants who are born with this, it means that they can't maintain temperature control, they can't maintain moisture control. It's a horrible disease, and then for adults who have it, it's like having really bad atopic dermatitis for the rest of your life. And so what our 17725 does is it replaces that SPINK9 protein, and it's actually 1 million times more potent than SPINK9, so we're very excited about this opportunity. There is another company, Daiichi Sankyo, that has a similar product in their pipeline. Our goal is to have something that is differentiated through superior dosing, and we'll see about efficacy as well. We expect to get into the clinic later this year, and then to start generating patient proof of concept data in 2025. Got it. For what that study could look like and what initial data next year could look like, is there anything more on that you're saying? Yeah, I think the things to look for are gonna be what, what is our dosing profile? When do we get into first healthy volunteers? And then with patient proof of concept data, that could come later, as soon as later in 2025. Got it. And maybe a question on DME and kallikrein inhibitor avoralstat, which has lower solubility than berotralstat or ORLADEYO. Can you talk about the strategy with this program and why the suprachoroidal injection makes sense here? Yeah. For DME, diabetic macular edema, kallikrein has been implicated. There's a lot of evidence that kallikrein plays a role in DME. Avoralstat, as you mentioned, is a really potent, very effective molecule, just has low bioavailability. So it didn't work as an oral drug for HAE, but those very properties make it kind of the right drug, right target, and then we have a partnership with Clearside Biomedical, with an auto-injector that gets the drug into the suprachoroidal space, which basically means avoralstat can sit in the back of the eye, dissolve very slowly, kind of like a natural depot, and inhibit kallikrein, which we think has the potential for, particularly for patients who are not helped by VEGF inhibitors in DME to help improve their vision. We'll be getting that into patients in early 2025. Got it. I think we're pretty much out of time, but, well, I guess for DME, if you get it into patients in 2025, so potentially have data in 2025 as well, or? Potentially later in the year, or in early 2026. Yes. Got it. Okay, and maybe to close out, if you can remind what your cash position is and anything else you want to highlight that I forgot to ask? Sure. I think we ended Q1 with $338 million in cash. As I said up front, we are on track to be profitable. We'll actually have operating profit this year. Next year, by the end of the year, we'll be cash flow positive and earnings per share positive, and then fully cash flow positive and earnings per share in 2026. So with growing revenues from ORLADEYO, being independent of the capital markets, and having a robust and growing pipeline, it's a really exciting time for us. Got it. Thanks for joining us today, Charlie. Thanks a lot, Maury.