Everyone, I'm Brian Abrahams, Senior Biotech Analyst here at RBC Capital Markets. Our next featured company is BioCryst, represented by their CFO, Anthony Doyle, and their SVP of IR, John Bluth. Well, thank you guys so much for being here. Yeah, thanks for having us. Okay, so I would love to learn a little bit more about the latest or the day-to-day dynamics that you guys are seeing. You're coming off of a very solid first quarter. Tell us a little bit more about the demand trends, the growth trajectory that you guys are seeing on the ground. Yeah. Just as a reminder, we'll be making forward-looking statements. Those statements have risk, and you can find our risk factors on our website. Overall, really, really, really strong. In Q1 and Q4, it was the strongest quarters that we've seen in patient prescriptions since the first two quarters of the launch. We highlight that to make sure people understand that the launch continues full pace. What we're seeing is that as doctors and patients have more experience with the drug, some of the growth that we're seeing, some of the awareness that we're seeing for the drug is becoming more and more organic. The team still does a good job of making sure that awareness is high, that willingness to prescribe remains high. But the more experience, the more patients we have, the more doctors that have experience, the more willing they are to try additional patients. So that's been phenomenal to see. The growth that we have seen outside of that over the past year has been phenomenal, hence the 30% quarter-over-quarter increase Q1- Q1. Prescriber base continues to expand. The market itself, we're still seeing 50% give or take in terms of switches from other prophylactic treatments and then 50% from patients who are new to prophy. There's still that many patients out there only on demand. Yeah. So historically, 50/50, 60/40, it's probably 70/30 at the moment. We see it going to 80/20 and maybe beyond there. But if you're using acute or rescue medication only, a first prophylactic treatment to try, ORLADEYO is super well-positioned for that to be a good opportunity for you. And then outside of that, ex-US within that continues to be strong. And ex-US, getting into more and more markets, seeing them mature, whether it's ourselves or with our partners, continues to be a strong opportunity for us to have that be a meaningful part of the billion-dollar upside. What are you guys seeing with regards to patient retention, and how has that evolved since the beginning of the launch? Yeah, very consistent. So within the first 12 months, retention rate at about 60%. For patients who are on more than a year, significantly higher than that. And again, same dynamics whereby for patients who do discontinue, they usually discontinue early. And usually for one of the two main reasons that we've talked about previously, either perceived lack of efficacy and less and less now kind of the GI side of the house. A lot of the education work that we've done with patients and doctors plays out well there to the point where, and Charlie talked about this last year, we're seeing a significant number of patients come through ORLADEYO a second time, maybe believing or trying to ascertain, did they stop too early and could have gotten through and been in a good place? Do you have any sense of the retention among those patients? Nothing that we've shared, but I'm sure we will at some point. Okay. Yeah. Regarding the conversion from free to paid drug for patients on ORLADEYO, it seems like that went a bit better than expected in the first quarter. Can you maybe outline insights from this latest re-enrollment period? Are there any trends that you're seeing with regards to commercial and public plan patients and maybe how those shape your expectations for the rest of the year for the copay assistance program and free drug? Yeah. So the continued work that we have done is the commercial team expanded probably this time last year, not only in terms of the reps, but also patient assistance, the work that we were doing on market access with a view to making improvements to our free-to-paid conversion. What we continue to see is on the commercial side, it's really strong about 80%. And we can make incremental improvements, we believe, from there. The Medicare side of the house this time last year was the challenge for us with the charitable foundations kind of not having sufficient money to provide assistance for reimbursement for Medicare patients. No better, no worse this year. But with the changes to the Inflation Reduction Act from next year on, where it goes down to at a pocket maximum of $2,000, then you can spread it over a 12-month period as opposed to paying them one fell swoop, we'd expect from that period onwards to be able to improve those paid rates. And then in Q1 specifically, we've talked about historically the challenges that we see in the reauthorization process, copay assistance, but the learnings that we've had, the work that we've been able to do with doctors, patients, etc., to move through that faster, that's what resulted in the guidance that we gave at $85 million and getting to $89 million in revenue for the quarter. That was the biggest change and the biggest success that we had within that period. And we think it's repeatable in later Q1s. We also hope that it can help not only in reauthorization, but in authorization in general. That's great. What about the uptake dynamics in Europe? It sounds like you're hopeful still that this will contribute a meaningful portion of your billion-dollar sales goal. Obviously, prophy and HAE has not been as widely adopted historically in Europe, so there's maybe different challenges there. And I know channel effects can make it hard to gauge what a true underlying growth trajectory looks like. So can you maybe talk about how the recent launches are going in regions like Spain or Argentina? Any other prospective markets that you're most excited about? And where do you see this? When When do you foresee this contributing even more meaningfully to sales consistently? Yeah. ex-US in general has been going really, really well. So Europe is going to be that biggest share. And so the biggest successes we've had thus far, France, Germany, U.K., Nordics, we got to the point where Spain and Italy and Benelux, etc., can play a more meaningful part. There's challenges there that are different, right? Prophylactic usage is significantly less. Androgen usage is far more prevalent than here in the U.S., for example. You've got to get through approval, then you've got to go through market access, sometimes federal, then regional, then hospital level. A lot of hospitals. So market access can be a challenge. But overall, the work that the team has done is phenomenal, continuing to grow at pace. It'll kind of, I think, compound upon itself where you're talking about multiple countries that are coming online at different points in time. And then you've got how mature each of those markets are and then our success within each of those countries. So the speed to peak for that area will probably be kind of after the U.S. But all of the opportunities that we've had and the challenges that the team have faced, we feel really good about the spot that they've gotten into. In terms of where next, yeah, a lot of Western Europe is done. We're in Japan. We're in Canada. And then partners in places like Latin America, Central Eastern Europe, Middle East. There's a lot of countries in the mix there. We recently announced Mexico approval on Monday. So excited to just get into more and more of those countries and then be able to take the learnings that we've had from other countries where we've launched and see success in those countries with our partners. How do you envision globally the evolution towards billion-dollar annual run rate for ORLADEYO? Can you talk about some of the, I guess, the puts and takes there and what it will take to get there in terms of sales infrastructure, pricing, free drug, and access improvements, demand growth? What's sort of the what's the path to get there? And how confident are you? Yeah, very confident. More confident than we have been given the continued success that we've seen in the product. So if I break it down into U.S., it's about $800 million of that billion with ex-U.S. being $200 million. How do we get to $800 million from where we are? I would look at three specific areas. So more patients on ORLADEYO. Last year, we had 321 net new adds. We need to average out at 200 a year for the next kind of 5 years, give or take, to get closer to that 2,000 patients that we think we need at peak. It'll be more than 200 in the near years. It might be less than 200 in the out years. So it won't be a linear $200, but feel good about getting there, especially based on where we were in the last 2 quarters and where we've been prior to that. Then it's the movement in free drug to paid. We think we can make improvements both in the commercial side, but specifically on the Medicare side is where we'd like to make the most significant impact there. And then some minor price increases along the way, I think, are very indicative of how you could get to that $800. We will pull all the levers that are available to us to get there and to get there as fast as we can. But feeling really good about the $800, tail end of the decade. And then that sounds weird to say when it's about 5 years off, but in the next 5 years or so. Outside of the U.S., it's going to be as and when we add those additional countries. So again, not just the approval, but the reimbursement discussions are often the trickier part. Those markets are generally less mature in terms of patient identification, treatment with other treatments like androgens, like we talked about. But on an aggregate basis, the more we can get into those countries, the more the team can identify opportunities to manage. Those are going to be volume plays. Pricing-wise, you're talking about 4 or 5 patients, XUS, to get to one patient here in the U.S. So we need to get into those countries. We need to see volume play out. But what we've seen thus far is very much in line with our expectations and very hopeful for what we'll do in the future. Got it. Great. And then as we look towards the future landscape in HAE and future competitive dynamics, how do you foresee ORLADEYO being positioned in a landscape where there may be additional orals entering the market in prophylaxis, as well as in on-demand, additional longer-acting injectables? What does your market research suggest might happen once some of these additional competitors enter? Yeah. I mean, for a long time, uniquely placed, right? We are the only oral. We will be the only oral for some point in time. Now, I think the acute usage may come first with an additional oral. There is another oral that it'll be, if that gets approved by the time it does, 7-8-year head start for us. And even then, for ORLADEYO patients who we talked about the discontinuation rate, for those patients who it doesn't work, they're not willing to sacrifice efficacy for convenience. So they go on to somewhere else. But for the 60%, for the patients who are on, they have efficacy that, based on the work that we've done on real-world evidence, based on what we see from those patients, just as good as anything else that's out there, just as good as injectable treatment. And then the convenience of a once-a-day oral, what is a target profile or what is a drug going to bring to market that's going to displace those? If it ain't broke, don't fix it, right? For a number more years of building that base up, we feel that we're super well-placed both now and in the future to be super strongly placed within the market. Over these intervening years, as the competition comes, we're taking advantage of that lead to deploy more real-world evidence, more outcomes data, and just build the brand and the awareness and the confidence of doctors, payers, patients. If other entrants, whether it's injectable or oral, are going to be banging the drum on not as much efficacy because all these drugs are going to work, but it's going to come down to a reduction in the burden of treatment, there is no drug better placed than us. How do you see the pediatric market playing out? I know you're running the APeX-P pediatric trial. I guess, what does the pediatric market look like overall? Yeah. No, it's been going great. The enrollment was honestly faster than even we had anticipated, I think indicative of the strong demand that exists within the market for something better, which our product will be very targeted to that age range. Injectables are out there, but we could have went with a once-a-day oral that was a pillar capsule, but having the granule formulation makes it even easier, more bespoke for that patient set. About 500 patients within that 2-12 or 2-11 age range. And again, given what we see in the adult side around efficacy and given the ease of use of our drug, we'd expect uptake to be fairly significant for our product. Remind us the timeline for. Yeah. We'd look to file next year. Great. Maybe looking at the broader pipeline beyond HAE, what should we be looking for with regards to 10013? Are you guys planning to disclose those detailed data? And what are sort of the key things that you're going to be looking for to determine the potential next steps, I guess, go, no-go for partnering this out? Yeah. There are really two potential next steps with 10013. One is that we find a partner who wants to take the program forward, and the other is that we don't. If we don't, then we'll discontinue the product. The reason a partner makes the most sense for this program is that it's an oral complement inhibitor. The complement space right now is really being led by Novartis and iptacopan. We can see the dataset and the indications that they're going after. For this product to compete there, it really needs broad, heavy investment. An outside party is much better positioned to do that and make the drug competitive than we are. We're on track to have data from the ongoing trial of 10013 middle of the year. We'll then share that with partners. We started talking with interested partners at the beginning of the year. They're interested in seeing the data. So are we. And once they have a chance to see the data middle of the year, we'll be able to announce where we are with the program by the end of the year. Okay. So are these data that would be publicly disclosed, or is this something that you'll be likely next disclosure will come whether? The next announcement's likely to be we have a partner or we've discontinued the program. Okay. Got it. You guys have highlighted a lot of other earlier-stage interesting pipeline candidates. I guess at the end of last year, you had an—I guess it was maybe December—you had an R&D day where a lot of these were first got revealed. But you've also been very judicious about how you've allocated your capital to make sure you're maintaining investment and maximizing the commercial opportunity for ORLADEYO as well. So I guess, what's your latest view on how you balance internal R&D investment versus commercial investment? And I guess, are there certain de-risking points in early development that would prompt you to make a larger investment in these earlier-stage programs, or will those sort of continue to run in the background because of the risk profile and because of the success you're seeing with the late-stage asset ORLADEYO? No, it's not the moment. There's been no compromise, right? So the strength of the revenue coming from ORLADEYO, the discipline, to your point, that we've had around investment in these assets combined with our strong balance sheet puts us in a spot where we can make the necessary investments in both ORLADEYO and peds and the rest of the pipeline and move as fast as we can to get them to their next stage without in any way jeopardizing this path to profitability that we laid out and are moving quickly towards. We do a lot of work at the start. So as much as we went through our R&D day, that doesn't mean that that's all there was, right? There was trimming prior to that to select only the assets to move forward that we thought were going to have a strong probability of success and add meaningful value to the company. We will continue to take that approach, right? So we get a couple of assets into the clinic in the next 12 months or so. And as and when we're generating data, we're constantly thinking about those guidelines that we laid out of best in class and first in class. And are we generating data that would support those assets moving forward? If it doesn't, then we will not move forward. If it does, then we work within the confines of the rest of the portfolio. How are we supporting it via revenue and cash? Where are they all playing out within their own development timeline? I'd love to have a problem at some point where there's too much in there that's too far advanced. And how do we pay for that? That would be a great problem for us to have. And whether it's a partner or we'd figure it out. But the depth and the breadth of that pipeline in terms of the indications, the drug targets, the mechanism of action, I think the risk profile that we have across the portfolio is really strong at the moment. Have there been any assets that have maybe moved faster than expected or accelerated more or that you've become more excited about in that early-stage pipeline, I guess, since they were all unveiled or even where the spaces have evolved such that you're more excited about the prospects, even if the data hasn't necessarily advanced yet? I think it wasn't that long ago. Everything is moving for the most part in line with how we had anticipated. Moving very quickly, testament to the team getting to the point where by the end of the year, we should have KLK5 inhibitor in the clinic and next year have avoralstat in the clinic. Then the ability to generate data for ourselves, for patients in the coming months, quarters, and years puts us in a great spot. The one that moved a little faster, Brian, Anthony mentioned, was the pediatric program with the fast development. Yeah. That's right. Yep. right. Yep. Got it. I guess, how do you determine, I guess, moving things forward on your own versus partnering? Are there certain indications, maybe like Netherton, that may be more in kind of your guys' commercial wheelhouse whereas others, like some of the ophthalmic diseases, that may be better suited for a larger party? Most of the focus that we've had is either rare disease or a rare disease-like market, which DME plays into in terms of the concentration. So while not rare, it looks rare when you're talking to KOLs and doctors. We'll continue to look at it. If we can utilize something else to go better, faster, increase the probability of success, increase the potential for value creation, we're all ears and we'll do the right thing for the asset and for the company. But at this point in time, we feel super comfortable moving all of these forward to their next phase. Okay. Great. Well, I know we're pretty much out of time. So Anthony, John, thank you guys so much. Great to see you and appreciate all the insights. Thank you, Brian. Thanks, Brian.