Okay, that's fantastic. Okay, great. Good afternoon, everyone. Welcome back to the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the Biotech Analysts here at the bank. It's my pleasure to have with me our next presenting company, BioCryst Pharmaceuticals. Sitting up here on stage with me are two members from the management team. We've got Babar Ghias, who is the Chief Financial Officer, and Sandeep Menon, who is Chief Research and Development Officer. Gentlemen, thank you for making the trip out west. Thank you, Tazeen, and thanks for having us. Maybe as an overview, just give us a quick description of BioCryst as it stands today. Some people know it in various different forms, but talk to us about what you found appealing about it because you're one of the newer members to join the company. We could talk about some of the important drivers of the stock after that. Fantastic. Well, thanks again for having us. Before I begin, I'll just remind that we will be making some forward-looking statements. I encourage you all to look at our SEC financials for the GAAP to non-GAAP reconciliations as well as risk factors. With that behind us, what attracted me to BioCryst? It's a company at a phenomenal inflection point. ORLADEYO has, you know, it's in sixth year of launch and continues to do extremely well in terms of how we're building that market, especially in the face of several approved products in the space. That naturally the safety of a growth engine behind a lead product that really excited me. Then what happens after that? I think if you look about the decisions that we have made in the last nine months that are pretty reflective of how the strategy is evolving behind ORLADEYO. Our vision really is to build a high-growth, innovative rare disease biotech with multiple products on the market by 2030. You know, when now that we're very fortunate to have navenibart, which is a phase III program in our, you know, in our pipeline. Back in navenibart, we have another very interesting and promising program in Netherton syndrome, no approved therapy, highly devastating rare disease. I think all of that, and then, you know, basically with Sandeep just very recently joining us. Hopefully, he shares the same enthusiasm in terms of the inflection point. We are at a very interesting and position now to take all the momentum that we have behind from ORLADEYO to channel that into building like next, you know, product candidates and then also, you know, converge them with our internal discovery pipeline. Historically, BioCryst used to only rely on internal engine. Now we're in such a strong financial position based on ORLADEYO's momentum that we can be much more creative in terms of building a really diversified, rare disease biotech. Okay. You guys have also really been busy with business development. How do you make a decision that some asset is worth bringing inside the company? We can start off with the Astria acquisition. We can also talk about some of the partnering decisions that have been made recently as well. Yeah. I'll just give you. You're absolutely right. In the nine months that I've been here, we've been really busy. I'll start with what sort of started this, what was the catalyst. We, as a small biotech company, had built a really good team in Europe. What we soon realized that one product was not going to be enough to build scale basically as a single product company, right? We were very fortunate that, based on the stuff that we were doing over there and the momentum that we also had in ORLADEYO in Europe, we were approached by NG to divest that business at very attractive terms. What that enabled us was to actually clean up our balance sheet and improve our financial profile because Europe, even though top line was increasing, like I said, we were not at scale yet that we could make profit out from there. That kind of freed that space on our U.S. financials to become much more profitable than we already were. That enabled us to bring in Astria Therapeutics. Like I said, at this point, it's with the vision of having multiple products by 2030. It was not going to come from an internal pipeline given that's early in nature. We knew that we had to do something. Astria was something that we had actually been looking for many years because there was such a natural synergy of having the only oral in the market and potentially the best-in-class injectable product with the same commercial organization. That made a ton of strategic sense as well as financial sense to bring those two together, and we were very lucky to have that in our portfolio. Moving on to what happens, we were never going to build in another European thing. We went through a process where we had a lot of interest because of how promising that program is from European buyers. After a careful evaluation analysis, we thought that it made sense to actually put it back in NG's hands because, you know, you don't want two brands to be competing against each other, and there's harmony around the brand promotion strategy. Most importantly, it is a team that we had curated over many years. We had a very high conviction in the NPV value of that deal. That kinda how it came about. To your next question, I think I would say that how we think about the decision, we while our first and second asset are in HAE, we are not an HAE-centric in the sense only an HAE company. We view ourselves as a broad rare disease company. Naturally, the first product is in HAE. The second one is coming in HAE because we didn't wanna take that risk. Netherton syndrome is a classic rare derm disease. When we think about business development strategy, we're looking at a broad portfolio. At this time it makes sense for us in terms of the infrastructure that we have built and the leverage that we have in business to look at more later stage opportunities, because I think we don't want to take like early development risk on something new because there's also a balance sheet perspective that we have to think about. As we think about our BD strategy and think about what comes next, it will tend to be late stage. It will tend to be with a potential product candidate that gives us an opportunity to bring more stuff into the 2030 time frames. Okay. On Astria, this is an injectable. When this drug launched before you were a member of the team, the main distinction was that this is an oral. Everything else is an injectable. An HAE for prophy. You know, this was something that's going to be differentiated, which is proven to be. Yes. You know, how did the thinking evolve that if you needed a second asset that an injectable, you know, less frequently injected of course. Nonetheless, one that was an injectable would be complementary to what you already have? Absolutely. I think we are in obviously many ways the pioneers of the switch market in HAE because it is predominantly a switch market as you've had experience as well. Now, if we go back in time and said that, you know, if the first approved therapy was an oral therapy, there will be more people on oral today than there are on injectables. I think the way the market has evolved, you had recombinant therapies, you had C1 esterase replacement therapies, you know, plasma kallikrein inhibitors. The way it has evolved, the way we see the market today, there's a structural segmentation. There are patients who don't mind basically taking a daily pill, and there are patients who, you know, who basically are okay with an injectable. I mean, the proof is, goes back to the stickiness as well to some extent. There are still patients who are taking CINRYZE as inconvenient a therapy as that is. It's an IV that you have to go through. I think the way we see the market, there are patients who want the oral and are okay. Then, injectable where, you know, by our count, there's about 5,000 patients on injectable, and several approved therapies. There's an incredible amount of demand for a, you know, an injectable that is dosed less frequently. I think that's where the value proposition we see of navenibart. [TAKHZYRO] has a, you know, in terms of our work that we've done and we've, you know, if you show it to docs and they look at lanadelumab, they look at navenibart blinded profile, and they're like, "Yeah, this is a fast-acting lanadelumab with less injection site pain." We feel that, you know, with right now we have the only oral in the market. By the way, for peds, I know Pharvaris is upcoming with the thing. In the peds, as you saw last year, we got the peds approval as well. We're the only product oral formulation with two and up approval. That we will have for many years. We will also have the best-in-class injectable product when potentially navenibart gets approved. We see that as complementary based on how the market has evolved over time. Okay. As ORLADEYO continues to mature, you know, what's your view of what peak sales could be by the end of the decade? Yeah. I think, we have laid this out very clearly, or at least I hope we have laid this out clearly in our investor deck. Before we had sold our European business, we had said that it is on a billion-dollar peak potential, and Europe was contributing. At that point in time, we did not have pediatric in our portfolio. We got rid of the European business. Now we have pediatric, which is an incredibly interesting market dynamics in terms of how it is doing that. From this point onwards, you know, we feel that we need to be doing about 150 patients. Net patients on average, b etween now and 2029 to get to that billion-dollar mark. To put things in context, historically, we've been doing over 200 net patient adds every year. We feel that it's not going to be linear, but it's very achievable. Like I'll give you a stat that, you know, in the most recent quarter, we continue to not just see like, you know, high prescription demand. Sixth year of launch, we're still adding new prescribers, which is pretty impressive when you think about, you know, 'cause historically, we used to give that stat. It is in line with the historical numbers. We're very excited that we're still adding new prescribers and kind of like how we're growing that market. You know, I think we're still maintaining that long term, it's that $1 billion path is highly achievable. Okay. As you think about the evolution of the competitive landscape for prophylaxis, you mentioned Pharvaris. How do you think about the market with another potential oral that can come on? Yeah. I, again, going back to the evolution of the market, this is not a winner-takes-all market. I think it's like you understanding your patient base. Naturally, the one thing that I would say, people that take HAE ORLADEYO- ORLADEYO. ... they are extremely well controlled. Either it works for them, or they move on because there's so many approved therapies- Yeah. ... you know, that are already there. We are not, nobody's insulated from more competition. You know, as we see it, and you know it, that we do extensive market research. We do every competitor the best product profile, and we do this sort of Monte Carlo simulation analysis. We feel that, you know, when we, when Pharvaris gets approved, we will, for new patient adds, we will see competition. If you're already very well controlled on a once-a-day pill, I don't know what more that another once-a-day pill adds because our data, and we generated this long-term data, that there's one thing is a regulatory endpoint or regulatory marker that we had of efficacy. But what's the real-world experience of patients? You know, the data that we've generated, these patients get over 90% attack rate reduction and then also mid-95%, mid-90%s compliance because it's working very well for them. We feel that the base business is very well protected. The new patient adds, yes, we will be competing for sure. The other thing is we'll have eight years of launch by that, launch experience by that time. Knowing our patient audience really, really well will matter a lot. Can I add something here? Sure. There are two other, two or three things that, you know, Babar nicely summarized, right? One is based on the real world data. What we are seeing is it's almost like a functionally, you know, mean attack rate of zero, right? Functionally, patients are fine, you take the medicine. Second thing, as a physician, as a prescriber, why would you change something just for some point estimate, you know, when you have got history with seven or six years of data and such a big safety database, right? That would be the, at least the two trigger points for us. Basically, that this is going to be, for us, an increasing market. These are the, there's only so many physicians, you know, that are prescribers. For them to try things new on a new patient, I'm not saying that will not happen. That will also happen. It may not be as much as what, you know, it's made out to be, you know, at least based on my experience as both as a prescriber and a, yeah, and a clinical developer here. Yeah. Okay. What about other mechanisms of action? For example, you know, there's gene editing that's being explored for HAE. How would you consider that falling into the competitive landscape? Yeah. Gene editing. To me, when I'm thinking about gene editing here, Tazeen, is basically you just have to wipe out and almost get to a full cure, right? Not only just functionally, but the mutations are out of picture in terms of, you know, in terms of the treatment. At least, again, I don't want to comment on Intellia data. But the expectation of a gene editing or a gene therapy would be that it is full, not only functional cure. A full pathological cure. I don't see that yet in terms of the data. For a prescriber and also for an insurance to pay that money for something that, you know, with the pill or others that are fully controlled, and many of these gene editing or gene therapy will have a longer commitment for safety database because we still don't know what's happening in the system. That's some... es pecially in a therapeutic area where you have got so many different options. It's not an option. It's not like Huntington's disease or somewhere where you don't have much options, right? Here, people have got a lot of options. To me, I'm still pretty mixed about gene editing and gene therapy, at least for this indication. Okay. Well, let's talk about your own pipeline product with Astria. How do you think a less frequently dosed injection could compete against orals? Maybe how are you thinking to the point that you made, unless it's curative for gene editing, how do you think that argument could change with an infrequently dosed injection? Just remind us what the dosing frequency is gonna be. Yeah. It is basically, and Babar, you have to add- Sure. ... more. This is just to remind people, it's my fifth week here. You know, from a perspective of what you get from the injectables, right? I think at least the injectables that are in the market, it's much more frequent. That's number one. The second one is also they have got high ISRs, you know, injection site reactions are much higher. What we are bringing is once in three months therapy, number one, in terms of convenience. The second one is a tried and tested mechanism that we already have been very successful. The third one, the mechanism actually implicated in the disease. Thirdly, we are bringing in, you know, less ISRs based on whatever data we have. We don't have a lot of injection site reactions. We are bringing in that profile for convenience, safety, and also mechanistically much more closer to the site of action. Yeah. The only thing I would add is, you know, when we do a lot of market research, the tipping point is three months. With six months kind of like, you know, a nother add-on on top. I think going from 12 injections a year to 24 injections that are currently with like, you know, different things versus four injections or possibly two injections, is a game changer. You're seeing some of that same analogs in, call it myasthenia gravis, where, you know, there's a lot of incumbent therapies. The newer ones are, like, more longer- dated. Yeah. Our market research showed that that is a huge game changer. Like I said, this market is such-- there's such segmentation that it's not just an oral or it's not just an injectable, it's based on real world experience. You know, patients are okay with taking injectable. I think the benefit and the beauty of navenibart is you get and forget. That's really what we're really excited about in this space. Okay. Just remind us when the next dataset is due? Dataset for? Navenibart. Yeah. It's going to be end of year, n ext year, is when we are going to do the BLA filing. BLA filing at the end of next year. Yeah. In terms of guidance of when top-line data happens? Top-line data would be around that time. Basically, it all depends upon. We are also discussing with the FDA in terms of, you know, what should be the right time to diverge the data. We want to make sure we are absolutely compliant regulatorily to, you know, to disclose any data, you know, outside, because this is a phase III pivotal study. As you know, we have said that by middle of this year, we will be enrolled. Yeah. What we have been extremely pleased with, that even with this acquisition, we did not skip a beat in terms of execution. It is the largest HAE study. Naturally, it's the first one of its kind in the sense there's a three-month dosing and a six-month dosing. You know, prior to that, you know, when Astria had been guiding, basically it was Q1 of 2027. I think we're still working with the FDA because of this dynamic of six months and 12 months. Six-month dosing, yeah. What it doesn't change is our BLA timeline. I think what we want to make sure is that we are compliant with FDA's requirement for this six-month dosing. Yeah. We are able to do the right thing for the trial. I think, you know, that's something that we are working on. Yeah. It's a unique data package where you have got in the six months, which everybody has done. We have got 12 months. We are in a real advantage. It's not only to Babar's point, not only the largest study, but also the longest study in HAE. What would be good data in terms of attack prevention? You know, I want to make sure that we are not hung up in like point estimates. Sure. What our current point estimate is, you know, 90%-92% is basically what we got in the phase II study. Obviously, between phase II, phase III, there is always going to be some- Yeah. ... translation that happens. It is going to be a randomized trial and everything. You know, Tazeen, what I mentioned before, it's the whole totality of the data. It's not just the point estimates. As a physician and a prescriber, people will not care whether it is between, you know, 90% or 80%, 85%. You know, people will care about, you know, what you bring to the table in terms of the convenience. Is my injection site reactions basically going down? At the end of the day, whether patients it's helping the patients or not. That would be the way we look at it. You know, it's a high probability that we'll be hitting the clinical meaningfulness in terms of, you know, what we have already seen, right? I think just to add on to that, what the industry... th ere's a regulatory benchmark, 90%, 92%, which by the way, we were really, really excited that thi rd and three-month and six-month is not differentiating. The other stat is worth noting is the attack, 0.16 attack per month, which is basically going to that. I think that's becoming more and more relevant that how well controlled I am. That's, you know, equates to less than two attacks a year. I think that's kind of like the durability of the potential drug candidate with the long-term, you know, dosing profile. I think that's what we're really excited about. As it relates to breakthrough attacks for patients that are on prophylaxis, do patients tend to be heterogeneous? Like, what is an average number really mean of attacks per year? It all depends on the patient population. Basically, you know, what we have started, at least our trial, the way it is designed, is making sure it is absolutely contemporary in terms of, you know, the average of attack rates have gone down over the year, right? Our screening period or the run-in period, we have got a criteria to screen in the right set of patients so that we are not... fi rst of all, it's much more of a precision approach in terms of having the right population in the study. Obviously, you know, to your question about heterogeneity, there is always going to be heterogeneity in response, you know. We are trying to do our best in terms of enrolling the right set of patients in terms of filtering through our run-in period. Okay. On the pediatric front, can you talk to us about the granule supply disruption? Absolutely. Where that stands? Absolutely. Just to clarify, it's not a safety or efficacy issue or an FDA issue. It's a very isolated quality batch release issue that we found a little bit late in the process as we were getting ready to ship product and just out of prudence, and you just get one chance to get your launch right. We wanna make sure that the patient experience has been, you know, is really, really good. You know, where we stand overall. We're still working on that root cause analysis, we will have more information in Q2. But it's not something that is requires like, you know, a engagement with the agency or anything like that. I think it's just a quality specs issue that we were just trying to solve for, which we'll have more information. Having said that, as you know, we have four strands. We have been receiving prescriptions for all four strands, which is very good. There's a lot of excitement for, you know, this product. What we are able to do in the meantime is collect the prescriptions and then, you know, our really strong patient services team can actually start the background process with respect to insurance verification and all of that. Once we actually have product supply, you know, we're ready to go. Scripts are still coming in. Th ey are coming in at, like, a really nice clip. Okay. How should we be thinking about nuancing, you know, second quarter versus third and fourth as it relates to this issue? Absolutely. Just to remind you, when we provided guidance at the beginning of this year, $625 million-$645 million. Peds was actually not a meaningful part of that guidance, and allow me to explain why. Because there's a paradigm shift that we have to go through in peds, and I just wanna make sure that, you know, we were a little bit conservative on that because we haven't seen that paradigm shift when we put the guidance. What that means is there's about 500 diagnosed patients in peds. I think our estimates show that there could be double that population that could, you know, as you know this quite well, you get one drug approved, and all of a sudden the net widens. There's about 5,500 patients. It's more tilted towards acute than prophylactic, which again, going back to the HAE origin days, you had more acute versus less prophylactic. Now, it's flipped over. I think there's two opportunities: A, more increasing the size of the patient population. You know, these are, you know, our APeX-P trial showed that the onset of symptoms starts as young as, like, 2.5 to three years of age. Parents actually delay the decision because they don't want to find out. They come back and they say, "Yeah, my kids were showing the symptoms of HAE, but I was delaying that decision." I think there's a huge opportunity to increase that. Naturally, you know, this basically this flip from acute to more LTP therapy. The fact that we are the only, right now for two and up, there's only TAKHZYRO approved, which is obviously has a lot of ISRs. This convenient dosing formulation will be a huge advantage. Again, 2026 is not going to be a big contributor, but it is part of our plan as we go to that $1 billion potential. You know, and to your point on Q3, Q4, we can't wait to be on the other side of it because the demand is good, and we'd love to see that those patients get converted into paid patients. Okay. Maybe let's spend a few minutes just talking about pipeline. You've got a Netherton's program. Just remind us where you are on that and why mechanistically it makes sense to look at it. Yeah. I'll start with the mechanism first, right? The mechanism here is KLK5 is implicated in Netherton syndrome. Number one. The second one is whether this is still a severe skin condition, we need to make sure that the drug is reaching the skin. What we have shown in terms of our healthy volunteer study that it is reaching the areas of interest where the target actually is. The third one is now we are testing it on the patients. We have completed a small clinical kind of a, you know, dosing kind of study kind of a thing, which is our part three. Now, we are starting to do our, you know, POC trial, where we will be actually measuring the real clinical endpoint up to 12 weeks. That's the, you know, a 12-patient study. It's on track to deliver the end of the year. It's the POC results basically. We will stay tuned. You know, hopefully, we will have some good news to share. Okay. Just remind us of what the data needs to look like in order for you to move forward with it? Also, was this an expensive study to run, just trying to get a sense of, you know, the type of investment the company wants to be taking on internal pipeline right now? Sure. What good looks like, there is nothing in there for these patients. If you look at these patients and you talk to them, they have got such an unmet need. You know, for them, even any improvement is supposed to be, you know, very clinically meaningful. I'm not to say that we will not be aspiring for more. We'll definitely look for a meaningful change that is clinically impactful for the patient, helping the patient quality of life. In terms of your... What was your next question, Tazeen? The investment there. The investment that you've made in the past. Yeah. Yeah. I think you can share on that. Yeah. I think it's not a very expensive study. I mean, naturally it's a fusion protein, so there is some CMC. The other thing is there's nothing approved- Yeah. ... for this patient population, so you also wanna be making sure that you have proof of clinical activity before you take the next r ound of, you know, high investment. I think, to Sandeep's point, by the end of the year, one way or another, we'll know if we have a product. What gets us excited is if there is clear signals, you know, naturally, as you've seen more of the recent rare derm, there is, you know, precedence that things can move pretty quickly. I think that's when we feel that, like, if we actually have a product, then we can naturally expand because we'll have potentially another product candidate that could get, that could hit our profile before 2030. So- It's really underdiagnosed as well. Yeah. It's underdiagnosed population. Outside of Netherton's, would you consider looking at other derm indications? Yeah. I think, you know, this goes back to, you know, the overall strategy. I think we have built this engine. You know, people think that it's just the commercial uplift, right? I think launching a drug is just an entire organizational uplift. We've already built that, you know, the an enormous, phenomenal patient- centric commercial organization. You know, this is a classic rare disease. Much like how HAE was, people thought 2,000 patient, whatnot, market continue improve. Are there other adjacencies, whether it's rare derm or other rare autoimmune diseases or inflammatory pathways? I think we're open to, like, looking at that. Now with Sandeep, who just joined us, we'll basically try to just define our strategy a little bit more crisply. Okay. If we think about the rest of the pipeline for the company, what other things do you think investors should be looking out for? I think, as you know that, in terms of, like, how our new evolution, the one thing that we want to emphasize for investors is, we want to make quick decisions. As you saw avoralstat, I'm not saying whether it was quick or not, but we decided that, hey, this is not a viable path forward. You mean in diabetic macular edema? Exactly. It's not a rare disease indication. This is not something for BioCryst to basically develop, and especially in light of the landscape development landscape. I think what we are very excited about the two programs right now. What we will be going forward doing is just being very disciplined about, you know, what we bring to the market next, whether there's a white space or there's a product differentiation, and, you know, be very crisp about, like, what we can actually deliver from our pipeline. I think for now, I would encourage to focus on our two lead programs that we have. Th en naturally, as we evolve our pipeline, we'll provide more updates. Okay. Last question, what's your view on external business development bringing in assets? You know, it's, if you think about our-. Beyond Astria. Beyond Astria. If you think about our three-leg strategy that we have, just to remind everybody, ORLADEYO has a very long durational IP. The composition of matter is September 2035, and the composition of matter on the base salt is up to 2040. We're not adding a lot of. We're not actually, our commercial infrastructure is steady state. Add on to that navenibart, it's the same commercial infrastructure whose, that IP goes until 2042. Over the next several years, we will be generating a lot of cash. We are already a cash flow generating business today. We are progressing these assets. The third is like, you know, what do we do for cash? Every capital allocation strategy, whether it's new business development, late-stage assets, and, you know, either even potentially like, you know, buybacks of shares could be on the table in terms of how we deliver that. I think BD will be a core part of our strategy to complement some of the internal and external. The one thing that I would say is, like, in the short term, we are not adding risk from a BD strategy because I don't think that will sit well at the stage of the company that we are at. Yeah. Okay. You were gonna say something? No. Okay. I'm completely aligned. Okay. Usually R&D leaders are not. Okay. Good to know. All right. Well, we're out of time now, so thank you for joining us. No problem. Appreciate you making the trip over. Again, we're looking forward to continuing to working with BioCryst and looking for the next data updates and launch trajectory continued. Thanks everybody for joining. Thank you so much for having us.