Good afternoon, everyone. Jonathan Wolleben, Citizens JMP. Thanks for joining us for day one of our life sciences conference. Pleased to have the team from BioCryst Pharmaceuticals here. We have Chief Communications Officer, John Bluth, and Chief Financial Officer, Anthony Doyle. Thanks, guys, for joining us today. Thanks for having us, John. Yeah, thank you. So I think most people who are paying attention know what you guys are focused on. But maybe at a high level, because you guys are adding a lot more things to the stable, at a high level, can you talk about the strategy and what you're working on at BioCryst? Sure. So just as a reminder, we'll be making forward-looking statements. Those statements contain risks, and you can find our risks on our website. So the focus is primarily on three things. The first is maximizing ORLADEYO. So we look to bring value to our company and our shareholders by maximizing the opportunity that is ORLADEYO and making that a billion-dollar drug. Secondarily, advancing our pipeline, and finding within there the next opportunity to bring to the market, and then doing it all while being fiscally responsible and moving on a path towards profitability. That's the main focus for the company at the moment. And that's where you get into trouble or not. That's, that's where we get into trouble, and it's also where the fun happens, so. And let's talk about ORLADEYO for a while because that's, you know- Sure ... your commercial product. It's doing very well. Can you talk a little bit about the HAE market? You know, we've seen, you know, the numbers. It's a, I think, the poster child for rare disease drug development. Drugs continue to grow the market, continues to get bigger and bigger. Your drug, ORLADEYO, has done very well. What do we know about patients on prophylaxis, prophylactic therapy today- Mm ... and how you guys are doing as far as getting into that market? Yeah. So overall population, around 7,500 patients, diagnosed and treated here in the US. The prophylactic/acute split is around 70/30 at the moment, 70% prophylactic, 30% acute, and we see it continuing to evolve to kind of more that 80/20, and we'll see where it goes from there. In terms of our place, you know, only oral in the market. At the end of last year, we announced that we had about 1,100 patients on paid and free product here in the US, so. Pretty early on, you guys have benchmarked that you want to hit $1 billion in peak sales. Sure ... which is a number that, you know, we like, investors like. It's a blockbuster drug. Yep. But you guys came out pretty early in saying that, and but then you actually gave us a roadmap- Mm ... on how you get there. Yep. Can you talk us through, you know, you're three years into the launch, I think? Yep. And then you're projecting out another six or seven years. What did you see that gave you that confidence, and can you walk us through how you get there? Yeah, we knew we believed we had something special with ORLADEYO. And so, you know, in the first year, we did $120 million, $122 million in revenue, and I think the projection at that point in time from the outside in was about $34 million. We lean heavily in on data. Not everyone was at $34 million. You were better than some others. But we lean heavily in on both historic data and the market research that we do. So if we look at the $1 billion, we break it down into the US market and the international market, and for the US market, we look for about $800 million, and for the ex-US market, about $200 million. In order to get to the $800 million here in the US, what do we need to do, right? That has evolved kind of over time, depending on what our base is. And so Charlie and the team did a really good job of explaining, I think it was at the end of Q3 last year. What we're looking for is about an average out of about 200 patients over the next kind of 5 or so years to get us into 2029. That provides the base for that increase, combined with an improvement in the free to reimbursed product, and then some minor price increases over that point in time that get us to the $800 million. Last year, our net new adds were about 321 patients, so it won't be 200 average every year out for those five years. Mm-hmm. In the earlier years, it'll be north of 200. In the outer years, it'll be less than 200. But the work that the team has done, and you've met Jinky Rosselli before, our head of data, data insights. The work that her team does in forecasting where we get to, and I think the accuracy that the street has seen in terms of how we've guided this year, has been pretty phenomenal, pretty on point. So, just back of the envelope, if we think 7,500 patients, 80% on prophylaxis, call it 6,000 for round numbers. You add 500 a year... 200 a year for 5 years, that gets you to 2,100 pa- You think you, at peak penetration, take a third of patients on the prophylactic market? About 2,000 patients, give or take, is what we're looking for. Okay. Yeah, to get to that $800. And to kind of, the track record, you guys had a really strong Q1. Can you talk a little bit about, you know, what led to that, you know, outperformance? Yeah. The biggest thing was all the prior work, all of the quarter-over-quarter-over-quarter growth that we've seen in the commercial team. That's what got us from kind of Q1 of last year, around $68 million, to Q1 of this year. Included in Q1 of this year versus where we had previously guided, the team did a phenomenal job of advancing and accelerating some of the work that they've done around pre-authorizations, co-pay resets, et cetera, which got us up from the $85 that we were initially projecting up to $89 million. But overall, it's just been... You know, Charlie's talked about the strength of the last two quarters that we have had in terms of patient adds, being the strongest that they've been since the very first two quarters at the launch.... Just continuing to see that progress quarter-over-quarter, that's what provides the drive. In any typical, like, the dynamics or reasons that those recent two quarters we're seeing more patient adds, are these patients that haven't gone to see their physician in the last couple years? Or or, like, is it more prescribing from the same docs- Yeah ... or more docs prescribing than you had before, or any kind of similarities or learnings? It's a little bit of everything. So one of the overriding things that we're seeing is that we continue to push out a lot of real-world evidence. We continue to have more and more both doctors and patients who have experience. With that experience comes confidence, right? They're not looking for only efficacy or only convenience, they're looking for both. Mm-hmm. And there's a significant portion of the population who find both in ORLADEYO. So as doctors have more patients that they're seeing seeing success with, they're more likely to prescribe or suggest that it be prescribed to other patients. And as more patients interact with other patients who are doing well, it's just a kind of ground swell of experience that leads to more and more patients getting on the drug. Can you talk a little bit more specifically about the real-world data? Because that was the rub early on from critics, is that the efficacy profile in phase III wasn't as competitive as the injectables, and no one wanted to try it. Yeah, yeah. What we always heard from physicians is, "My patients just want to try an oral and then see what happens. Sure. Can you talk a little bit about the experience that- Yeah ... is going on in the real world? Yeah, so we've always said that the drug doesn't work for everybody, right? So what we have seen is, for those patients who it does work, it works really, really well, as well or better than anything else that's in the market at the moment. And so getting to the point where that efficacy is, you know, in line with anything else with... that we're seeing, that the number of, or the attack frequency is generally low, again, as low as we're seeing with anything else. And having more and more patients see that, more and more doctors see that, that's what gives us confidence in getting where we need to get to. You know, it's... Again, there are patients for whom it will not work- Mm-hmm ... and I think that's, you know, patients who will find some other drug, that'll work for them. But we would encourage all patients to give it a try, and to, you know, try and see if they can find success on this drug. 'Cause when it works, it really, really works. Do you have a sense, if you have 100 patients start, what percentage would do well versus don't? Generally, what we've seen is, within the first 12 months of a patient trying it, around 60% stay on drug through that 12-month period. Once we have patients on for 12 months, the discontinuation rate from there is really, really low. You mentioned in Q1, you know, reauthorization was a key point to that outperformance. Can you talk a little bit about the patients coming on ORLADEYO? You know, who's switching from a different drug, who's starting, who's naive? Is one of those paths easier for you guys to manage or, you know, insurance to manage? I don't know that either one is necessarily easier, 'cause they'll all use similar insurers. But generally, we're seeing about 50% of patients historically come from acute usage on-demand therapy, and then 50% coming from prophylactic switches. Mm-hmm. A lot of the work that the team has done is, you know, working with doctors in their offices in terms of education as to, you know... I'd rather take a little bit more time to get an approval the first time, than try and rush through as many as you can get to and just get any answer, even if the answer is no. So making sure that whether it's blood work or anything else that the insurers need, that they're getting it right the first time. I can't recall, have you guys gave an update on time from, you know, start from a request to paid drug? I think we've given one in a little while. It's, you know, historically, it's been somewhere between a month and two. Mm-hmm. Again, the focus is on getting it right the first time. It's not necessarily the speed to a yes or no, it's the speed to a- Mm-hmm ... preferred, yes. Yeah. If we need to take a little bit more time and make sure everything is dotted and crossed, then that's the approach that we'll take. And then I think you guys reported, correct me, two weeks ago, or was it last week? It's all a blur. Two weeks ago or so, and you guys gave us $97 million Q2 - Mm-hmm ... and we're five weeks in, six weeks in. Mm-hmm. How can you give us such an exact number that early in a quarter? We have a strong base at this point in time. We have a sole source specialty pharmacy who works with all patients to distribute product, and we've been very accurate historically. So at this point in time, we think that $97 million is a really good number for Q2. And then remind us how you revised 2024 guidance. Yeah. So we revised the bottom end of our range up. It was 380-400, it's now 390-400. You know, you had a really good start to the Q1. How does that trickle down to the rest of the year? Does it make it that much easier? Is it... You know, you didn't revise the top end up- Sure ... but is there any headwinds, tailwinds throughout the rest of the year? It seems like the Q1 is the hardest, but I, you know, I don't know. Let us know the inside baseball. Yeah, no, you know, it gave us enough confidence to move the bottom end, the range up, and again, we feel good around that 390-400. What could move it from here? All of the normal key factors. How do we do in terms of net new patient starts? How are we working with the, insurance companies in terms of speed of authorization? What are we seeing on the DC rate? But a lot of those factors have kind of normalized to the point where that 390-400 is very achievable for us. How, and you know, I think we talked about this the other week. How frequently do you guys update your market research to make sure your numbers are fresh, and you're getting the right... Like, with a combination of the demand from the specialty pharmacy versus your projections, and how do you marry those two? Yeah, I mean, in-house, all the time. In terms of the work that we do externally, you know, every quarter, Jinky's team is doing some work, and then every year we do a major refresh with a very robust patient set. Is it 170 doctors or- Mm-hmm or so that we're looking to get insights, and the trending and what we're seeing has been very consistent year-over-year. Mm. Now, it's evolved as there have been- Mm ... you know, new, potential entrants to the market. But overall, it's what's given us confidence to give the guidance that we've given historically, and then hit those guidance numbers. The target is 200 net patient adds per year. You know, you know, what does that look like as far as added versus lost? Does that matter at all? Are you adding 400, losing- Yeah, we haven't given specifics as to the absolute variations, but again, 321 net new patients last year, and Charlie's showed historically the trending and, you know, monthly on- There's some wobble, yeah. ... adds versus discontinuations. There's peaks and troughs, and there's some spikes. But generally, the two lines are moving- Mm-hmm ... kind of very much in a stable manner. So again, 321 last year. It won't be 200 every year. This year we'll do more than 200. Mm-hmm. And then once you get into a kind of 2027, 2028 timeframe, yeah, it might be less than 200, but ultimately gets us to where we need to be from a peak side. Hey, I guess in the near term, you know, what kind of wiggle would start to worry you on the downside? Like, is it 150, is it 100? You know, 320 is a great number, but you didn't rise upwards, which, you know, I think is the right move. Yeah. You know, does any number start worrying you if it hits earlier than the 2027, 2027 time frame? Nothing that we have seen, and nothing that we are forecasting. Mm-hmm. You know, if we got to a certain point, we've prided ourselves on giving accurate guidance. Mm-hmm. So what we've said is, as and when there's adjustments, whether it be up or down, we will make shareholders aware. But at this point in time, the robustness of that growth has been phenomenal to see, and we expect it to continue. And we've shared a couple pieces of information that add to our confidence there. One is what Anthony mentioned, that in the last two quarters, we've added more new net patients than we have since the first two quarters of the launch. So the patient demand continues to be very strong, and as we do our forward-looking market research, which has been very accurate, doctors continue to look forward a year and say, "We expect to continue to grow the ORLADEYO share of our business considerably. One dynamic that we talk about every so often, but you know, Inflation Reduction Act and its impact. You guys talk a little bit about the indirect impact on you. Can you walk us through what that looks like next year, and you know, different push and takes, and how it could affect ORLADEYO sales? Sure. Last Q1 of 2023, we talked about how the Medicare population from a reimbursed rate had gone significantly down, and that was due to, you know, insufficient funds available for charities to support patients who couldn't who needed support in order to afford maximum out-of-pockets, co-pay, et cetera. What we're seeing this year is, you know, no worse than it was last year, and hopeful that next year, once the out-of-pocket maximum does two things: it goes from $3,250 down to $2,000, and then it hits where instead of having to do that in one fell swoop, you can pay it off over a 12-month basis. Mm-hmm. That the affordability for both patients and the amount of money that the charities have, and how far that will spread, could be meaningfully impactful in terms of we have a high approval rate. Mm-hmm. For those patients who are on Medicare, we need to increase the reimbursed rate. Now, what will insurers and PBMs do in the background? Mm ... to balance where those funds come from? We'll see. But from a volume side, we're hopeful that the Inflation Reduction Act can help patients to better afford those drugs. So it'll just be a more better prediction of the budgets for everybody on their end? Correct. Got it. Okay. A lot in the US there, EU expansion, approvals, seems like every week or so we had Mexico. Sure ... today, I believe. Yep, yep. Yep. Talk us through, you know, how things are going ex-US, the key drivers there, if you want to get to $200 million peak. Mm-hmm. I don't think you guys have talked about that roadmap as concretely, but, you know, big picture, what can you tell us? Yeah. It's still earlier in its development, but to your point, you know, we've got approval in a lot of countries, whether it be in Western Europe, Japan, Canada, working with partners in Latin America, Middle East, Eastern Europe. The intent is to just have a steady drumbeat of approvals, market access, and launches in those countries. In terms of the 200, I mean, the biggest market opportunity that we have there is Western Europe, and the team there have done a phenomenal job in places like UK, Germany, France, expanding into Italy, Spain, Nordics, et cetera, to just work with those authorities. You know, you get approval, but then market access and pricing negotiations are the harder part of that. But the team there is doing a really, really good job to get patient adoption, and it's a different market, right? It's not as mature. The prophylactic use is not necessarily as high, so there's some work to do, not only in terms of what we're doing to get the market, but the maturation of those markets. I remember years ago, EU austerity was a huge issue for HAE drugs. Has that changed at all as we've gotten more real-world data and utilization in other markets? Are they starting to come around, or are they still making it quite difficult for access? They're still very prudent and careful about where they spend their money, and so what we have said previously is, for, you know, patients on an ex-US basis, you're looking at about four to five patients to get you to the value of one here in the US. Do you think that becomes, you know, the time, later timing to peak in the ex-US market, then, to get to the $200? I think it'll take... Yeah, it'll take us a little bit longer ex-US. Mm-hmm. you know, we're not yet in all of the countries we want to be in, and so we'll need then some history, and there'll continue, I think, in those countries, to be an evolution of the move from whether it's acute via, you know, current acute medications or, you know, steroids or whatever the current treatments are there, into a more prophylactic-centric market. There'll continue to be evolution for probably longer than there will be here in the US. So we have great trajectory in the US, beating expectations. We have ex-US geographic expansion, but also label expansion on the horizon. Mm-hmm. Can you talk a little bit about, you know, how you're expanding into younger patients? Yeah, the pediatric opportunity is really exciting. So the opportunity to bring a drug that's tailor-made for the pediatric population... You know, we looked at it, and obviously there's an injectable that's available there. I have young children. Getting them to swallow pills is no mean feat either. So being able to have a formulation where it's granules, and we're trying to make it as easy for that population to take the drug and then see success on it as possible. We'd look to get, you know, a filing in next year, and look to get approved then as quickly as we can, and the market is exciting. Not only... You know, it's not a huge opportunity in terms of patient size, maybe 500, in that 2-12, but the opportunity to get more families, given that it's a hereditary disease, to have awareness and experience of ORLADEYO, we hope can have not only the impact of growing that market, but also the kind of halo effect that you would have in terms of familial usage. With limited options in that younger age group, is there, like, an urgency from a parental perspective? Like, "Not my child, I don't want any worries," as far as prophylactic acute split, but there's not options there quite yet. So any sense what that looks like? Well, well, we saw enrollment in this trial move extremely quickly- Mm ... faster than even frankly, we expect, and I think that really speaks to the need and the interest that parents have- Yeah ... in getting their children access and helping this drug get to market as fast as possible. It's... Yeah, it's certainly a different dynamic. And then you guys are projecting out to 2028, 2029, and, you know, looking at what today looks like tomorrow, but then also we have, you know, a pretty competitive pipeline of assets coming through. Can you talk a little bit about how that factors into your forecast, if at all? Sure. And then, how ORLADEYO stays competitive with newer entrants? Yep. No, I... Listen, we are very, you know, paranoid in the work that we do. When Jinky's team does market access, you know, we are, I think, very conservative around the profile that we give our drug and, you know, much more generous about the, what we, what we show for other, potential entrants to the market. And despite that, we see, you know, continued strong uptake in ORLADEYO. We'd have, you know, if you're looking at the next oral prophy, you know, seven to eight year head start on, on that product. So by the time they get to market, we will be much closer to our peak, and at that point in time, what we said is for where ORLADEYO works, it works really, really well, as well as anything else that is available in the market from a real-world evidence and what we're seeing from our patients who are on drug. So what's gonna displace that? You know, what, what would be disruptive, and what other manufacturers are gonna bring to the market that would get those kind of sticky, well-treated, well-tolerated patients off our drugs? We feel really good about where we'll be at that point. And we're using that head start to really build the brand and add brand experience. So we're not just taking ORLADEYO around the world to new markets, but we're also publishing more and more real-world evidence- Mm-hmm ... publishing more and more pharmacoeconomic, health economic outcomes research, and that's adding to the confidence that doctors are gaining with the drug. And I think you're seeing that in the momentum that the launch is generating. So, you know, we've got an opportunity to give patients what they want, which is maximum convenience and maximum efficacy with one pill once a day, and they get that with ORLADEYO. The real-world evidence, the long-term data, shows a 90% reduction in attack rate, that's as good as all the other drugs there. So when the drug works, it's really reducing or eliminating attacks- Yeah ... and patients love it 'cause it's a capsule once a day. I guess the other important thing to mention is, you know, you're mentioning a peak around 2028, 2029, maybe 2030. What's composition matter on ORLADEYO? Yeah, it goes out until 2039, so- Yeah, it's a long tail. ... a lot of years at that. And then an alley-oop for you, Anthony, path to profitability. Sure. Sure. I'm excited about, right? So in Q1, operating profit or operating loss, not including the non-cash stock comp that we have, was only $800,000. And so this year we expect to have an operating profit. Next year, towards the second half of the year, on a quarterly basis, EPS and cash flow positivity, and then full-year EPS cash flow and positivity for 2026. And with sufficient, you know, cash on hand and revenue generation and OpEx management during that time, that we're capital markets independence and don't need to raise any more money. Which I think is an important point that I'm not sure if people have glommed onto quite yet, and it seems like you're still not getting credit for the ORLADEYO success or the projections. And then you guys had a really good R&D day last year, talking about what's coming through. You know, do you need a couple early wins, and when could those happen? And how you think about, you know, pressing the gas on ORLADEYO but also funding that pipeline, is that baked into that profitability path? It is, it is. So ORLADEYO, we constantly look for opportunities to improve the markets, the work that the commercial team does, real-world evidence generation. The ORLADEYO Peds product, or project, is moving faster than we could have hoped for. And then on the R&D side, because, you know, some of it's earlier, we won't have, you know, significant phase III-type spend until the point in which we've surpassed that profitability marker. But in the interim, doing as much as we can to move quickly, and hence, getting into the clinic tail end of this year with 17-725, and then early next year with avoralstat. Like, those, those programs are moving at full speed. So you have two programs potentially in the clinic in the next two years, and then potential first in human readouts shortly thereafter? That's exactly right. We'll have healthy volunteer data or a study started this year with BCX17725, data next year, and then we'll be in patients after that in the avoralstat program, in DME patients. And then the other program to mention is BCX10013, which is going through a PNH trial right now, and we expect to partner that program or discontinue it, so we'll know that by the end of the year as well. And I guess last one to end on, how does that factor into kind of guidance for spend, the 10013? Does that just come off the books regardless? How do you guys think about that in terms- Yeah, it's, you know, regardless. We're not gonna move forward with its development. So to John's point, it's either partnered and somebody else will take that on, or it's discontinued as a program. But either way, from an OpEx side, it falls off of our books. Okay. Now, I'm excited 'cause we'll have other programs coming up behind it- Mm ... to start to generate data. But yeah, we, we factored into our guidance that 10013 won't be moving forward in our hands. Got it. Perfect. Well, guys, I always appreciate seeing you guys, and I appreciate all the hand-holding you do with the guidance. It makes our lives a little bit easier. So keep up the good work, and we're gonna look forward to tracking the progress. Yep. Thanks, John. Thanks, John. Thanks.