Welcome to the Wells Fargo Healthcare Conference. Before we get started, if you are a member of the press or media, please disconnect at this time. This is a restricted line. Any unauthorized party in this meeting or any unauthorized use of the information communicated in this meeting is subject to prosecution to the fullest extent of the law. Any unauthorized person, including the media, that is on the line at this time, please disconnect. Please note, today's call is being recorded. Great. Thanks, everyone, for joining us. I'm Jacob Hughes, specialty pharmaceuticals analyst at Wells Fargo. Next up, we have BioCryst Pharmaceuticals. From the company, I'm very pleased to have President and CEO Jon Stonehouse. Investors can email me questions via the platform, and I'll ask them on your behalf. Alternatively, you can just email me directly at jacob.hughes@wellsfargo.com. Jon, I'll hand it over to you to give a little bit of an intro on your progress, and then maybe we can jump into Q&A from there. Sure. Thanks, Jacob, and thanks for inviting us to your healthcare conference. Let me just make some real quick introductions of who's joining me. We've got Charlie Gayer, our Chief Commercial Officer, Helen Thackray, our Chief R&D Officer, John Bluth, our Chief Communications Officer, and Bill Sheridan, our Chief Medical Officer. We're all going to be making forward-looking statements, and those statements have risks, and you can find the risk factors on our website. In terms of the progress of the company, there's never been a more exciting time at BioCryst, and that's due to the fact that our strategy is really coming together. What we're good at is being able to make oral drugs for patients who suffer from rare disease, and that's really hard, as evidenced by the fact that there's so few out in the marketplace. Our team is excellent at it. The other piece that's really important is it's not some small incremental improvement in convenience that you think of in other diseases. In rare diseases, it's life-changing. It's a really big deal for patients. The evidence for that is the successful start of our launch with our first oral drug for a rare disease, ORLADEYO, for patients suffering from HAE. We can get into a lot more discussion around how the launch is going, but it's going extremely well. We've said that we expect no less than $100 million on net revenue this year, the first year of launch, and that's in COVID. We're not making any excuses because there's COVID out there, and there are very few rare disease drugs that have hit $100 million in their first year. It's off to a great start. Why is that? It's a really good drug, a great drug. We've got an experienced and very effective team, and we made a lot of investment to get smart, to be able to get patients to switch from other therapies to ORLADEYO. We're starting in the marketplace. We're generating revenue with ORLADEYO, and then right behind that is another oral drug for rare diseases, our oral Factor D inhibitor, BCX9930. It's in pivotal studies in PNH and then in three different indications for nephritis indications that are complement-mediated in a basket study. It's the equivalent of having three, or excuse me, four molecules in either pivotal studies or in proof of concept studies. Our pipeline is full and we're just getting started. There are many more indications to go after with BCX9930. Last but not least is the discovery engine continues to produce other molecules for oral drugs for rare disease, the next one is BCX9250, our ALK-2 inhibitor for FOP, a really horrible disease, a bone development disease, that affects kids and it's just very debilitating. There's a huge unmet need, bringing an oral drug in that space is big. I guess one other point that I would make is financially, we're in a really solid spot. We've got a drug that in its first year will generate no less than $100 million and continue to grow from there. We've said it's +$500 million, we're putting a lot of emphasis on the plus because that's an old number, we now have updated information. We've got other ways of bringing in capital like the debt and royalty that we did last December. Very, very exciting time, Jacob, to be at BioCryst. Okay, perfect. Thanks, Jon, for that intro. We can just start there on the launch. The first quarter, $11 million-$30 million, 2Q, it's really good sequential growth, and you're talking about $100 million, at least $100 million your first year. This is in a COVID environment, no doubt, just talk about what has gone right about the launch, how is it going, any more details around that. I think on the last call, you talked about 70% of the market have policies now on ORLADEYO. How would you frame that payer response? Charlie, you want to take that? Yeah, sure. What's going right? There are a lot of things going right in the launch, and I think that's, as Jon said, we're not making any excuses around COVID. We knew we were launching in COVID, I think our team did a great job preparing for that and really being able to reach customers in all different ways, including virtually. We launched in the height of COVID last December and January and still got off to a great start. To the extent that things get better on that front, I think it just creates more opportunity going forward. Some of the things we're really pleased about in terms of the early launch metrics is we expected patients to switch to ORLADEYO from other drugs, particularly injectable prophylaxis products, that's exactly what's happening. With 60% of patients in Q2 who are new to ORLADEYO switching from other prophylaxis products, and the remaining 40% switching from acute-only. The prophylaxis market is continuing to grow, and ORLADEYO is contributing to that. The payer process is really important. It's going well. What doctors and patients have told us is if we don't get that piece right, that would be real trouble, and they've seen difficulties in the past. The key there is the demand that the payers were seeing from patients really brought them to the policy-making table sooner. Our market access team is just really good at working with payers. To have 70% of patients having access to an ORLADEYO coverage by mid-year, that is way ahead of expectations for a rare disease launch. We expect continued success in Q3 and in Q4. That just gives doctors and patients more confidence going forward. Okay. Maybe just to add on to that. Consensus wasn't there at $100 million for the first year, no doubt, when you launched this drug. What do you think the Street got wrong? You mentioned there's still upside to the $500 million in peak sales. What's going to drive that? Is the payer piece something that was misunderstood? Maybe just some additional color around that. Yeah. Let me take this one, Charlie, and then if I miss something, you can jump in. I think what people missed was that what we said was this is a switch market and that we were going to get patients that were well-controlled on injectable prophy wanting to come on our drug, and they were going to do well, and they were going to stay on our drug. That's what we said 2.5 years ago, and people looked at the top-line results from our study and compared it to the top-line study data from other products, and they said, "No, that's not going to happen. Okay. What did we show you in the marketplace? That's exactly what's happening. 60% of sales or new start forms are coming from prophy switches, and 40% are coming from on-demand therapy. It's exactly what we expected, and the team has done a great job of executing on that. What gets us more excited is the bulk of this demand is coming from docs asking patients if they'd like to switch. We haven't activated the patient-to-patient, patient coming in asking the doc yet. Because of COVID, it's just harder to get people together. When we get that rolling, we expect that you'll see even greater growth in the future. There's some headwinds with COVID. We're not making excuses for it. We're very pleased with where we are, but the upside opportunity here is significantly higher. If people think they missed the window here, no way. We're two quarters in. It's only $100 million in the first year. This is a lot bigger. There's a lot more value to be created here. We're still just getting started, for sure. Okay. Will you look to update your peak sales estimate in the near future? What kind of forum would you look to do that? Yeah. I don't know exactly the timeframe, but you can figure around a year of launch experience is a good time to start to give people an idea of what the peak sales is. Like I said, it's an old number. We've been putting a lot of emphasis on the plus because we think it's bigger. Okay. Just on the launch, how many of your visits with prescribers is face-to-face versus still virtual? Putting that in context of, you talked about COVID challenges for this launch, and it's still going well. Can you hear me? Yeah. Yeah. We're good. Okay, perfect. Put that in context of what other challenges are you encountering that haven't been an issue hindering the adoption of this drug? Yeah. By Q2, the majority of our calls were in person, as COVID really improved broadly across the country. It also is very much a region, territory by [crosstalk] territory situation having a where the market is. We've been in a better place than we were back in Q1. We'll have to wait and see what happens with the Delta variant going forward. I forward. I think one of the challenges, Jon mentioned the locator program is not happening in person, and that's just a deferred opportunity. Okay. I think the other thing is doctors [crosstalk] haven't been able to get together in a broad forum and meet congresses the way they would normally. Yeah. [crosstalk] Doctor word of mouth I think is going to be really important too, as they start to realize how many of them are prescribing it and what kind of experiences they're seeing with the drug. Knock on wood, we'll be able to get back to congresses this fall. Okay, can you hear me? Yeah. Okay, perfect. Put that in context of what other [crosstalk] challenges are you encountering that haven't been an issue from both Takeda and others? What's been the response, and who are you taking share from? We're in the switching. We're taking share, we believe, in proportion to general market share. The number one product that is patients are switching from is TAKHZYRO, then HAEGARDA, Cinryze, and some androgen patients. That's what we expected. Those are all good drugs, but patients really appreciate the opportunity. Many of them appreciate the opportunity to control their attacks with a lower burden of therapy on an oral once daily. They're big companies. They're competitive. I think they've noticed us, and they emphasize their benefits, and we emphasize our value proposition, and we think that we'll continue to do well. Yeah, bigger is not better here, honestly. Doing smart market research like Charlie did to really understand how to get switches, bring in a product that patients really want, and then the size of this stuff is something a company like BioCryst can really manage. Being smarter is more important than being bigger. Okay. Fair enough. Maybe just on the ex-U.S. opportunity, you have a partnership in Japan. How are you thinking about ex-U.S.? Is that something you'd go after yourself, or would you partner that? Yeah. It varies from region to region. Let me just talk about it in general. In the contribution to the global peak sales, the way you should think about it is there's a number of patients we're going to get in terms of the 7,500 in the U.S. Then our expectation is that we're going to get a similar share in Europe and a similar number of patients in Europe, and a similar number of patients outside of Europe and the U.S. The price will be a lot different. It'll be a volume play in other parts of the world. You add them all together, and you can get to a meaningful number. Right now, we've got a partnership with Torii in Japan. We just felt that because that market was a little bit less developed, that it made more sense to have more resources to find patients. It's almost like the Cinryze days from 12 years ago. In Europe, Charlie's got a very experienced, talented team that's launching in Germany and getting ready in the U.K., France, and other parts of Europe. You saw this week that we've got a partnership with NewBridge, and we've got approval in UAE, and we're going to keep going around the world, continuing to get approvals, and it may be a distributor or partner, it may be a BioCryst team. It all depends on what value a partner brings versus us doing it on our own. Okay. Fair enough. Well, congrats on the launch. Maybe we can move to the pipeline. First on BCX9930. Can you just review the data on that program to date? Bill, you want to- Sure. We don't have time to go over all of the details, but for those of you who'd really like to do that, I'd refer you to our website at our March the 22nd R&D date. What we showed there was a really nice clinical benefit in terms of reduction in transfusions and increase in hemoglobin. The goals here are to control the anemia and get rid of transfusions, and both of those things help patients by reducing symptoms. Really pleased with the data. We had data in both C5 inhibitor naive patients with PNH and also patients who had an inadequate response to C5 inhibitor. Very consistent with predictions in terms of what a proximal complement inhibitor would do, an alternative pathway inhibitor. That information set us up to design pivotal studies, and we negotiated those with regulators, and we're now in the process of setting them up. Very strong data. Okay. How does that data in PNH compare to competitor data we've seen from Novartis, Apellis? It's hard to make direct comparisons, of course, across studies because of differences in eligibility criteria. I think that a fair conclusion would be all of the data emerging for proximal complement inhibitors in PNH is very encouraging for patients with the disease. We're very pleased with our data. Yeah. When you get hemoglobins close to normal and you stop seeing transfusions, it's hard to get a whole lot better than that. It's not a perfect drug, but the data's very impressive. Okay. I guess to add on to that, why do you believe patients on competing drug or Apellis would switch to 9930? Yeah. This is really interesting, right? It's repeating what we just learned in HAE, only it's better with complement-mediated diseases, and I'll use PNH as an example. The infusion burden there is times 100 what it is in HAE. Patients tell us they spend a half a day in the infusion center from the time they have to get tested, to the time it's got to be prepared, to the time they got to be infused. Talk about a burden. That's crazy. On top of that, with the C5 inhibitor, you have extravascular hemolysis, right? With the proximal inhibitor, like a Factor D inhibitor, you don't have that. We expect better efficacy at the end of the day. Charlie. He's already doing it. Gathering as much information as he can in the market to understand in the heads of patients and docs what makes a good switch, and how do we get people to switch. That'll be a competitive advantage when we get into the marketplace. Okay. All pressure on Charlie and the team. Lots of confidence in Charlie and his team. Lots of confidence. Of course. Maybe beyond PNH, what's your plan for 9930 and additional diseases which could complement it there? Helen, you want to take that one? Yeah, be happy to. With the work that Bill has done with 9930, we have a dose that is effective as a Factor D inhibition dose. We intend to continue to move forward an alternative pathway-driven disease. You've seen that with the introduction of our basket study for renal indications, looking at complement-mediated nephritis indications. There are a number of additional indications, either driven by the alternative pathway or for which the alternative pathway contributes to the disease, that we can continue to advance this molecule and assess for proof of concept and eventually for indications. Okay. Do you plan to partner this program? We haven't needed to at this point. Honestly, I'm really impressed by what the team has done thus far in terms of the speed. We went from a phase I study to a pivotal study in PNH. We're in four different indications or heading into four different indications this year. One of the reasons we brought Helen on is how do we scale this to manage, maybe triple that, right? I think we've shown that we can do this. It's a matter of scale. We'd always be open to somebody that can show us they can do it better than us. We haven't found that yet. Okay. Maybe frame it for folks, how big is the opportunity in PNH and what's the full scope of addressable diseases that you could go after? Charlie, why don't you talk about PNH first and then how you see the rest of the indications on a macro basis rather than one by one. Yeah. PNH itself globally, we believe is $1.5 billion-$2 billion, somewhere in that range. The full market isn't even addressed yet. That alone is a really attractive opportunity. Each of these additional indications that are rare diseases, some a little bit larger than others, each of them can be a billion dollars plus. The global opportunity for this whole portfolio could easily be $10 billion. Okay. There's a lot of room to compete here, and we think we've got a great product, and we're ready to compete in a lot of different spaces. Yeah. You get 10% or 20% market share on that, you got a $1 billion-$2 billion drug. Yeah. That's value. That's exciting. Okay. Well, maybe just on the pivotal trial for 9930, maybe walk through the design of that trial, the enrollment timelines, and some of the key catalysts that The Street should be looking for. Ultimately, what's your expectation for the readout of that trial? Bill, you want to take that? Sure. Very excited by these studies. We have two studies. The primary endpoint in both studies is change from baseline in hemoglobin. We're studying two populations with PNH that will be very nice to have in the label. The first population is patients who are on a C5 inhibitor, but not having an adequate response, and they're still anemic. That's going to be an open-label comparison to their current C5 inhibitor treatment compared to our drug. The duration of that efficacy component is 24 weeks. The second study is in people who are not on a C5 inhibitor, and that's a placebo-controlled trial, and duration of that comparison is 12 weeks. Overall, for an application for an NDA, we need to keep following patients on our drug for one- year. The overall duration of the studies is one- year. Okay. It's very exciting. We're in the process of implementing sites around the world in many centers, and we look forward to initiating patient enrollment this year. Okay. Maybe beyond that, Jon, you talked about additional areas you can go into. You talked about BCX9250 and a bunch of other different ways you can go. Maybe talk about how you're balancing all those priorities and maybe some additional details on what you could do. Yeah. It's mind-blowing, honestly. It's too early to share with you, but there's a lot going on, and there's a lot more molecules to come. That is the beauty of this strategy and the beauty of the drug discovery capability that we've built is that I can't even see the end to it. It's really impressive. It goes back to what I said about why we brought in Helen, not only to help us prioritize what to go after, but also how do we scale to go after as many of these as we can. When you start to move into the financial position that we're moving into with real revenue being generated by our lead program, it's a matter of just getting people, and our ability to attract people, good, talented people right now is the best I've ever seen. Okay. in my 14 years. That's why when we hear from folks that say, "We missed out," we're just getting started. The value here is really significant because of all the things we have, everything we've learned, and the great people that we're attracting to this company. Okay. Maybe just on the financial side of things. What's the runway you have now? What's the runway for your cash to. What milestones does that get you through? Yeah. What we've said publicly is that we've got cash to get us into 2023. As you can imagine, there's variables here. There's how much do we invest in 9930, and how much do we generate in revenue from ORLADEYO. Sure. I worry a lot less about cash runway now because of the fact that we're generating revenue. It just puts us in a different position, and then it also gives us access to sources of capital we didn't have before, right? Like debt, like royalty revenue or capital. We're in a really solid financial position, and it will only get stronger with time due to the successful launch of ORLADEYO. Okay. Maybe lastly, it sounds like a lot of this is organically driven on your drug discovery platform, but is there an interest as well to go out and license assets or whatever the case may be in varying stages of development across rare disease, or is that not an interest for you at this time? We don't need it, right? We have plenty to bring forward that can create real value, and it's under our control, right? We know the molecules because we made them. We don't have to due diligence on somebody else's- Yeah. worried about what we don't know, right? These are ours. It's based off a really solid strategy and a great team that understands structural biology. No, not really. The capital that we have or that we'll bring in, we're going to put into our own discovery and our own pipeline. Okay. Well, I think we're bumping up on time, we'll leave it there. I really appreciate you and the team's time, and congrats on all your progress, and good luck the rest of the year. Thanks, Jacob.